Overview of the Thalamus

Medical Neuroscience | Tutorial

Overview of the Thalamus

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of today’s learning, the student will:
1. Discuss the embryological origin of the thalamus.
2. Discuss the location of the thalamus in the human brain.
3. Characterize the role of the thalamus in brain function.

TUTORIAL OUTLINE

I. Embryological origin of the thalamus

A. the thalamus is a major part of the diencephalon, which is derived from the prosencephalon
(see Figure 22.3 and A242)
1. the dorsal and posterior part of the diencephalon becomes the thalamus
2. the ventral and anterior part becomes the hypothalamus
3. thus, the thalamus is a component of the forebrain

II. Anatomical localization of the thalamus

A. with respect to the whole brain: the thalamus is near the center of the forebrain (see Figure
A14C; Appendix BoxA (Figure A))
B. relative to the internal capsule: the thalamus is medial to the posterior limb of the internal
capsule (see Figure A14B)
C. relative to the lateral ventricle: the thalamus is the floor of the body of the lateral ventricle
(see Figure A14C)
III. Role of the thalamus in brain function
A. general organization (see Appendix BoxA (Figure A))

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 Overview of the Thalamus

1. comprised of a large number of distinct nuclei (circumscribed clusters of neurons) that

are bounded by a “Y”-shaped bundle of axons
2. each nucleus sends and receives projections for a different region of the cerebral
cortex:
a. anterior group (in the crook of the “Y”) projects to cingulate gyrus
b. medial group projects to the anterior frontal lobe in front of the motor cortex
(i.e., the prefrontal cortex), the insula and the medial temporal lobe
c. lateral group projects to different regions of the remaining sensory and motor
regions of the cerebral cortex in each lobe
d. additionally, there are smaller nuclei within the fiber bundles that make up the
“Y”; these intralaminar nuclei project diffusely throughout the cerebral cortex
B. principal functions (see Appendix BoxA (Figure B))
1. relay information, in a “feed-forward” fashion, to the cerebral cortex
a. sources of input to specific thalamic relay nuclei
i. for somatic sensation, from the spinal cord and brainstem
ii. for audition and vestibular sensation, from the brainstem
iii. for vision, from the sensory periphery (retina)
iv. for the modulation of movement, from the basal ganglia and the
cerebellum
b. outputs from specific thalamic relay nuclei to the cerebral cortex; these
outputs to the cerebral cortex terminate densely in layer 4 thus defining
unimodal, “primary” cortical areas
i. for somatic sensation, to the postcentral gyrus
ii. for audition, to the superior plane of the temporal gyrus
iii. for vision, to the cortex in the banks of the calcarine sulcus (lingual
and cuneus gyri)
iv. for the modulation of movement, to the motor cortex
2. distributer of higher-order (more processed) signals from one cortical area to another
a. some thalamic nuclei are driven primarily by cortical inputs, rather than
ascending sensory or motor signals
b. these thalamic nuclei, in turn, provide higher-order input that drives activity in
other (non-primary) cortical areas
3. modulators of cortical function
a. the intralaminar and midline thalamic nuclei (sometimes called the “non-
specific thalamic nuclei”) send diffuse projects to the cerebral cortex that
terminate diffusely in upper cortical layers
b. these diffuse projects have modulatory influences over large-scale networks of
cortical neurons that could be important for attention, arousal, mood change,
and transitions in sleep and wakefulness

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 Overview of the Thalamus

STUDY QUESTION
What are the functions of the thalamus?
A. articulate, compound and communicate
B. relay, distribute, modulate
C. amplify, coordinate and calculate
D. advance, compute and contemplate
E. amplify, compute and communicate

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 Overview of Cortex and Cortical Circuits

Medical Neuroscience | Tutorial Notes

Overview of Cortex and Cortical Circuits

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.
NCC8. Fundamental discoveries promote healthy living and treatment of disease.

LEARNING OBJECTIVES
After study of today’s learning, the student will:
1. Discuss the embryological origin of the cerebral cortex.
2. Discuss differences in the cytoarchitecture across the cerebral cortex.
3. Discuss the anatomical organization of the cortical microcircuit.
4. Characterize the “ACC” functions of the cortical microcircuit.

TUTORIAL OUTLINE

I. Embryological origin of the cerebral cortex

A. generation and differentiation of neurons and glia

1. nearly all neurons are generated by the middle of the second trimester; thereafter,
only very few neurons are ever generated in the CNS!
2. neuronal and glial genesis occurs in the ventricular zone of the developing forebrain:
the telencephalon, which is derived from the prosencephalon (see Figure 22.32)
a. cell division occurs against the wall of the ventricles where precursor cells
divide and produce other stem cells for many mitotic cycles (see Figure 22.7)
b. some are destined to differentiate into a glial precursors and others into
neuronal precursors, called neuroblasts
3. after many cycles of mitotic activity, some postmitotic neuroblasts migrate away from
the ventricular zone toward the developing cerebral cortex, called the cortical plate
a. many neurons in the CNS are guided to final destinations by glial cells that
span the distance between the ventricular zone and the pia mater

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 Overview of Cortex and Cortical Circuits

b. for the developing cortical plate, neuroblasts migrate along radial glial cells
(see Figure 22.12)

4. consequently, the cortical plate matures into the cerebral cortex in each hemisphere,
which remains a continuous “sheet” of neural tissue that becomes increasingly folded
into the outer surface of the forebrain

II. Anatomical organization of the cortical microcircuit

A. the continuous “sheet” of neural tissue in each hemisphere is actually multi-layered, with
different layers of neurons and intrinsic connections serving somewhat different purposes
B. the “canonical” cortical microcircuit
1. thalamus projects to (granular) layer 4
a. called “granular” because of the numerous small stellate neurons that are
found in abundance in this layer (see Figure 26.2A)
b. at low magnification, this layer looks like grains of sand (hence the term
“granular”)
2. layer 4 projects to upper (supragranular) layers (2 and 3)
3. upper (supragranular) layers project to lower (infragranular) layers (5 and 6), and to
other cortical areas, including corresponding areas in the opposite hemisphere
4. layer 6 projects up to layer 4, and back down to the thalamus
5. layer 5 projects to the basal ganglia (caudate nucleus and putamen), brainstem and,
for some areas, the spinal cord
C. in addition, there are local connections within each cortical layer
1. each neuron tends to project diffusely to its near neighbors
2. each neuron tends also to project to neurons in surrounding columns that have similar
functional properties (“like connects to like”)

III. The “ACC” of the cortical microcircuit

A. all this circuitry serves to amplify, compute and communicate

1. amplify thalamic input
2. compute additional functional properties that may not be present at antecedent
neural processing centers (e.g., the thalamus)
3. communicate information to other cortical areas and to subcortical centers (e.g.,
thalamus, basal ganglia, brainstem)
B. different divisions (areas) of the cerebral cortex have slight modifications of these basic layers,
which provides for the recognition of anatomical and functional distinctions across the cortex

IV. Cytoarchitecture of the cerebral cortex

A. “cytoarchitecture” refers to the cellular composition of neural tissue

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 Overview of Cortex and Cortical Circuits

1. recall that neural tissue comprise numerous different types of cells (neurons and glia)
that vary considerably in size and morphology
2. different locations in the cerebral cortex differ in subtle (and sometimes not so subtle)
cytoarchitectonic features
B. around the turn of the 20th century, several important histologists began to stain brain tissue
to reveal the cellular anatomy of neural tissue
1. one important figure in the history of cortical exploration was a German
neuroanatomist, Korbinian Brodmann (1868-1918)3
2. Brodmann studied cortical tissue with a stain that reveals the presence of cell bodies,
called a Nissl4 stain
3. Brodmann famously mapped the cytoarchitecture of the cerebral cortex proposing
some 50 or so divisions based on the cytoarchitecture (e.g., cell density, cell size, layer
thickness, radial organization of cells, etc.) (see Figure 26.2B; Box 26A)
C. differences in the cytoarchitecture of different cortical areas (and differences in the input and
output connections) are the basis for putative differences in the function of cortical areas; a
bold hypothesis proposed by Brodmann and still under investigation for most of the human
cerebral cortex

STUDY QUESTION
The “ACC” of the cerebral cortex is suggested as a useful way of remembering the principal functions of the
cortical microcircuitry. So do you remember? What is the “ACC” of the canonical cortical microcircuit?
A. articulate, compound and communicate
B. amplify, coordinate and calculate
C. advance, compute and contemplate
D. amplify, compute and communicate
E. atlantic coast conference

3
For more on the life and times of Korbinian Brodmann, visit his Wikipedia page by clicking here; and enjoy a unique artistic tribute to
his seminal work at website honoring important European neuroscientists, which you can find here.
4
In neural tissue, Nissl substance is rough endoplasmic reticulum; Nissl substance is found in cell bodies and in the proximal dendrites
of the largest neurons in neural tissue.

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 General principles of sensory systems

Medical Neuroscience | Tutorial Notes

General principles of sensory systems

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of today’s learning, the student will:
1. Discuss the organization of neuronal pathways in sensory and motor systems.
2. Account for the generation of action potentials in peripheral axons in response to somatic sensory
stimulation.
3. Discuss factors that influence how information is coded in sensory systems.
4. Discuss the concept of the receptive field in sensory processing.

TUTORIAL OUTLINE

I. Overview of sensory and motor systems

A. neuronal pathways
1. series of neurons that transmit information from one location (e.g., sensory surface) to
a distant target (e.g., cerebral cortex)
2. pathways may go in either direction; i.e., ascending from periphery “inwards” (e.g.,
towards cortex; typical of sensory pathways) or descending from cortex “outwards”
(e.g., towards spinal cord; typical of motor pathways)
3. nomenclature for neurons in a pathway
a. first order (primary) neurons
b. second order (secondary) neurons
c. third order (tertiary) neurons
B. all major sensory and motor pathways have midline crossings (= decussations)
1. although the evolutionary perspective on pathway decussations remains opaque, an
important principle of brain function is that each cerebral hemisphere receives sensory
information from the opposite side of the body
2. therefore, each ascending (and descending) pathway must decussate

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 General principles of sensory systems

3. but stay tuned … in a forthcoming tutorial, you will learn that cerebellar
representation is ipsilateral!
C. sensory transduction
1. sensory transduction: conversion of the physical (or chemical) energy stimulus into an
electrical signal in a sensory neuron
2. in the somatic sensory system (see Figure 9.22):
A. application of a stimulus deforms the skin and the sensory receptors
embedded within it
B. physical deformation of receptor membranes open ions channels, and sodium
ions (current) flows into receptor ending
C. current depolarizes receptor membrane producing a receptor (or generator)
potential
D. information coding
1. the quality of a stimulus is encoded by the identity of the activated peripheral receptor
(“labeled line” coding scheme)
a. different axonal endings respond to restricted sets of sensory stimuli
i. selectivity is explained by:
- morphological specializations of receptor endings
- properties of the ionotropic channels in receptor membranes
ii. selectivity is conveyed and preserved in parallel pathways in the CNS
2. strength of a stimulus is encoded by:
a. the rate of action potentials in the afferent axons
b. the temporal pattern of action potentials in afferent axons
3. adaptation (see Figure 9.4)
a. all receptors adapt (decrease their firing rate) to the persistent presence of a
stimulus
b. some adapt slowly and display tonic firing patterns as long as a stimulus is
present (more static qualities)
c. others adapt rapidly and display phasic firing patterns (more dynamic
qualities)
4. sensory threshold (see Figure 9.2)
a. all receptors have a sensory threshold for firing action potentials
b. in the somatic sensory system, “threshold” is the strength of mechanical
deformation necessary for producing a generator potential of sufficient
amplitude to elicit an action potential
i. some receptors have a low threshold (e.g., encapsulated endings)
ii. others have a high threshold (e.g., free nerve endings)

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Figure references to Purves et al., Neuroscience, 5 Ed., Sinauer Assoc., Inc., 2012. [click here]

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 General principles of sensory systems

5. receptive field (see Figure 1.13)

a. region of the body that when stimulated by a mechanical stress elicits a
response in a sensory neuron
i. the center of the receptive field general elicits a robust response
(either a sharp increase or decrease in the firing rate of the neuron)
ii. surrounding the center of the receptive field is a annular region (called
the “surround”) that antagonizes the center zone
b. receptive fields may be defined for any neuron in a sensory pathway
c. for primary neurons, receptive field size is inversely proportional to the
density of their peripheral processes (receptors)
i. thus, large receptive fields are created by large or diffusely distributed
sensory endings
ii. small receptive fields are created by small or spatially restricted
sensory endings
d. for neurons in the cortex, receptive field size is directly proportional to the
degree of convergence in sensory pathways
i. thus, large receptive fields are created by a high degree of
convergence as many inputs from antecedent centers converge on the
dendrites of a single cortical neuron
ii. small receptive fields are associated with minimal convergence of
inputs from antecedent neural centers
e. in mechanosensation, the differential sizes of receptive fields in neurons that
represents different parts of the body accounts, at least in part, for the
differences in two-point discrimination along the body surface (see Figure 9.3)
f. in the cerebral cortex, cognitive factors (e.g., attention, stress) may modify the
size and sensitivity of receptive fields

STUDY QUESTION
What explains regions of high sensory acuity, such as the center of vision or the tips of the fingers?
A. large receptive fields
B. sparsely innervated sensory surfaces
C. densely innervated sensory surfaces
D. small receptive fields
E. both A & B are important for creating high sensory acuity
F. both C & D are important for creating high sensory acuity

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 Mechanosensation

Medical Neuroscience | Tutorial Notes

Mechanosensation

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of today’s learning, the student will:
1. Identify and characterize the major sensory endings that mediate sensations elicited by touch,
vibration, proprioception, and pain and temperature.
2. Characterize the mapping of the body (somatotopy) in the primary somatic sensory cortex.
3. Discuss the distribution of somatic sensory signals to higher-order processing centers in the parietal
lobe, motor centers, emotional centers and memory centers in the brain.

TUTORIAL OUTLINE

I. Overview of somatic sensory systems2

A. two major, modality-specific subsystems: mechanosensation and pain & temperature
1. a specialized (phylogenetically newer) subsystem for the detection of mechanical
stimuli (e.g., light, discriminative touch, vibration, pressure, movements of muscles
and joints)
2. a more primitive subsystem (phylogenetically older) for the detection of thermal and
potentially harmful (painful or nociceptive) stimuli, and a more crude sense of touch
B. basic functions of somatic sensory systems:
1. identify shape and texture of objects (light touch)
2. detect potentially harmful situations (nociception = “pain perception”)
3. monitor internal and external forces acting on the body
4. contribute to neural representation of self (i.e., proprioception = “self-perception”)
C. basic organization of the somatic sensory systems:

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For completeness, pain & temperature systems are introduced here, but they will be considered in detail in a separate tutorial.

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 Mechanosensation

1. different types of peripheral receptors mediate the detection of different types

(submodalities) of stimuli in each subsystem
2. two sets of pathways:
a. for the post-cranial body (i.e., below the head and including the posterior
portion of the head)
i. mechanical stimuli: dorsal-column medial lemniscal system
ii. pain and temperature: anterolateral system (and an unusual visceral
pain pathway to be discussed later)
b. for face (and anterior portion of the head)
i. mechanical stimuli: pathway through the principal (chief) sensory
nucleus of the trigeminal complex
ii. pain and temperature: pathway through the spinal nucleus of the
trigeminal complex

II. Mechanosensory processing

A. cutaneous and subcutaneous mechanosensory receptors

1. general organization and function
a. first-order neurons are ganglion neurons (see Figure 9.13)
(i) cell body in dorsal root ganglion or cranial nerve ganglion
(ii) neuronal morphology = “pseudomonopolar”
(iii) diverse endings of peripheral process (axon)
(iv) central process synapses on second-order neurons in CNS
b. functional categories
(i) mechanoreceptors (touch, vibration, pressure)
(ii) nociceptors (pain)
(iii) thermoreceptors (temperature)
c. morphological categories (see Table 9.1)
(i) free nerve endings (pain, temperature)
- supplied by very small diameter, ‘unmyelinated’ C fibers and
lightly myelinated Aδ fibers
(ii) encapsulated endings (touch, vibration, pressure)
- very low threshold for activation
- specializations of large diameter, myelinated fibers
- differ in location in skin, the size of their receptive fields, and
their density in different locations on the body surface
d. mechanism of sensory transduction (see Figure 9.2)

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Figure references to Purves et al., Neuroscience, 5 Ed., Sinauer Assoc., Inc., 2012. [click here]

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 Mechanosensation

(i) physical deformation of receptor membranes open ion channels, and

current (carried by sodium ions) flows into receptor ending
(ii) current depolarizes receptor membrane producing a receptor (or
generator) potential
e. receptors specialized for tactile discrimination (see Figures 9.5-6 & Table 9.2)
[in Table 9.2 and Figure 9.5, for each of the four afferent systems described, learn the receptive
field size (small vs. large), location, sensory function, effective stimuli, and adaptation rate (slow
vs. rapid)]

a. Meissner’s corpuscles: nerve endings encapsulated by Schwann cell

lamellae
b. Merkel disks: saucer-shaped nerve endings that contact specialized
cells (Merkel cells) between the dermal papillae
c. Pacinian corpuscles: axonal endings encapsulated by a large set of
fluid-filled lamellae (like the layers of an onion)
d. Ruffini corpuscles: nerve endings surrounded by a spindle shaped
capsule
2. receptors specialized for sensing body position (proprioceptors): “self-receptors” that
respond to the mechanical forces arising in the body from the force of gravity and
from active movements
a. muscle spindles (see Figure 9.7A)
(i) small number of intrafusal muscle fibers surrounded by a capsule of
connective tissue in parallel with the extrafusal, striated muscle fibers
(ii) primary sensory endings from group Ia and group II afferent fibers
encircle intrafusal fibers
(iii) both types of afferent fibers are stimulated by stretch applied to the
muscle spindle
b. Golgi tendon organs (see Figure 9.7B)
(i) free nerve endings of group Ib afferent fibers that are woven into the
matrix of collagen fibrils in tendons
(ii) sense the force (tension) generated by muscle contraction
c. joint receptors
(i) mechanosensory afferents distributed around joints
(ii) sense joint motion
B. ascending central pathways for somatic sensation (see accompanying tutorial)

III. Somatic sensory thalamus (see Figure 9.10)

A. the thalamic division that processes mechanosensory signals is the ventral posterior complex
1. receives ascending superficial mechanosensory and deeper proprioceptive information
2. divided into two main nuclei

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 Mechanosensation

a. ventral posterior lateral nucleus: receives information from the body (below
the head) and posterior head
b. ventral posterior medial nucleus: receives information from the face (and
anterior head)

IV. Somatic sensory cortex (see Figure 9.10)

A. primary somatic sensory cortex: region of the cerebral cortex that first receives the inputs
from the (third-order) neurons in the ventral posterior complex of the thalamus
B. located in posterior bank of central sulcus (postcentral gyrus)
1. includes Brodmann’s Areas 3a, 3b, 1 and 2
2. each subdivision of the primary somatic sensory cortex receives somewhat different
submodalities of mechanosensory input
a. Area 3a: responds primarily to stimulation of “proper” proprioceptors (e.g.,
muscle spindles, joint receptors)
b. Area 3b: responds primarily to simple cutaneous stimuli applied to localized
skin surfaces (e.g., discriminative touch)
c. Area 1: responds to more complex cutaneous stimuli, often involving
stimulation of multiple digits in a certain direction
d. Area 2: responds to both complex tactile and proprioceptive stimuli
3. somatotopy in the primary somatic sensory cortex (see Figure 9.11)
a. each subdivision of the primary somatic sensory cortex contains a complete
“map” of the contralateral sensory surface
b. certain body regions that are especially important for function (hands, face)
are “over-represented”; i.e., receive disproportionate cortical allocation within
the body map (the same is true at subcortical levels)
C. higher-order somatic sensory processing
1. each subdivision of the primary somatic sensory cortex sends axonal projections to the
other subdivisions (see Figure 9.12)
2. these subdivisions, also project to several other important cortical regions:
a. a secondary somatic sensory cortex in the inferior parietal lobe, which itself
contains an entire representation of the body surface
b. the primary motor cortex in the precentral gyrus (and other motor areas in
the frontal lobe), where somatic sensory information is integrated to produce
to appropriate motor behavior
c. regions of the superior parietal lobe where a “schema” of the somatic self is
generated, based on the integration of somatic sensory and visual inputs (and
probably other sensory inputs); this is what is sometimes referred to as the
“body image”
3. higher-order somatic sensory areas project to limbic structures, such as the orbital-
medial prefrontal cortex, the amygdala and the hippocampal formation, where

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 Mechanosensation

somatic sensory information is integrated with emotional signals (implicit processing)

and memory traces (explicit processing)

STUDY QUESTION
Considering just the consequences for somatic sensation, what do you expect to result from a stroke involving
the right middle cerebral artery?
A. anesthesia over the left side of the body (face, upper extremity, trunk, lower extremity)
B. anesthesia over the right side of the body (face, upper extremity, trunk, lower extremity)
C. anesthesia over the left side of the body below the face
D. anesthesia over the right side of the body below the face
E. anesthesia over the left side of the body below the trunk
F. anesthesia over the right side of the body below the trunk
G. anesthesia over the left side of the face and left arm, but sparing the left leg
H. anesthesia over the right side of the face and right arm, but sparing the right leg

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 Mechanosensory pathways

Medical Neuroscience | Tutorial Notes

Mechanosensory pathways

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of today’s learning, the student will:
1. Characterize the organization of the dorsal-column medial lemniscal system from peripheral nerve
ending to cerebral cortex.
2. Recognize components of the dorsal-column medial lemniscal system in the spinal cord,
brainstem, thalamus and cerebral cortex.
3. Characterize the organization of the trigeminal mechanosensory system from peripheral nerve
ending to cerebral cortex.
4. Recognize components of the trigeminal mechanosensory system in the brainstem, thalamus and
cerebral cortex.
5. Characterize the organization of the neural pathways that mediate unconscious proprioception
(“proper proprioception”) from peripheral nerve ending to cerebellum (the spinocerebellar
pathway).
6. Recognize components of the spinocerebellar pathway in the spinal cord and brainstem.

TUTORIAL NARRATIVE

Introduction
There are two major, parallel systems that convey somatic sensory information from the periphery of the post-
cranial body to the cortex, the dorsal column-medial lemniscus system and the anterolateral system. There
are comparable parallel systems carrying information from the face associated with the central projections of
the trigeminal nerve. In addition, there is an important system carrying proprioceptive information from the
muscle spindles to the cerebellum. This tutorial will focus on the pathways taken by the components of the
systems for transmission of neural signals pertaining to the detection and perception of mechanical stimuli. It
is important for your understanding of neurological deficits seen in the clinic to know where these pathways
travel relative to each other and to other structures (including the cranial nerve nuclei) in the brain.

1
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 Mechanosensory pathways

Pathways mediating mechanosensation

The pathways that convey information about touch (especially fine, discriminative touch), pressure, and
vibration from the body and face are illustrated in Figures 1 and 2. In the dorsal column-medial lemniscal
system, which carries information from the body, the first order neuron is the dorsal root ganglion cell. The
first-order cells have peripheral processes that are often encapsulated (e.g., Meissner corpuscles, Pacinian
corpuscles) or are associated with specialized receptor cells (e.g., Merkel’s discs). They send central processes
into the spinal cord, where major branches travel in the dorsal columns to the caudal end of the medulla.
There, they synapse on neurons in the dorsal column nuclei, the gracile and cuneate nuclei.
The second-order neurons located in the dorsal column nuclei send their axons across the midline, where they
form a fiber bundle known as the medial lemniscus (hence, the name of this pathway). The axons of the
medial lemniscus run through the rest of the medulla, the pons and the midbrain before ending in the ventral
posterior lateral nucleus (VPL) of the thalamus. Third-order neurons in the VPL send their axons via the
internal capsule to terminate in the somatic sensory cortex, which resides in the postcentral gyrus.
The first-order neurons associated with receptors in the face lie in the trigeminal (Gasserian) ganglion. The
central processes enter the brain via the fifth cranial nerve and terminate in the principal (or chief) sensory
nucleus of the trigeminal complex (or of the fifth nerve). The second-order cells in this nucleus send axons
across the midline to form the dorsal trigeminothalamic tract, also known as the trigeminal lemniscus. These
second-order axons travel to the ventral posterior medial nucleus (VPM) of the thalamus. Third-order neurons
in the VPM send their axons to the postcentral gyrus.

Pathways mediating proprioception

Cutaneous receptors that feed into the dorsal column-medial lemniscal system are one source of information
giving us a sense of body position. A second important source of such information is the pathway leading from
muscle spindles. Two important targets of this information are the postcentral gyrus and the cerebellar cortex,
as illustrated in Figure 3.
The afferent fibers associated with muscle spindles in the legs send their central processes into the spinal cord
where they form synapses in a prominent nucleus in the thoracic and upper lumbar spinal cord, known as the
dorsal nucleus of Clarke. (The axons ascend in the dorsal columns from their point of entry until they reach the
thoracic cord, where they form synapses in this nucleus.) The second-order neurons in Clarke’s nucleus send
very large, heavily myelinated axons into the dorsal-lateral white matter on the same side, where they ascend
as the dorsal spinocerebellar tract. A major target of the spinocerebellar tract, as its name implies, is the
cerebellum. The fibers enter the cerebellum via the inferior cerebellar peduncle. Branches of the
spinocerebellar tract also form synapses on cells in or near the dorsal column nuclei, which appear to then
send axons into the medial lemniscus (joining the pathway already illustrated in Figure 1).
The afferent fibers associated with muscle spindles in the arms send their central processes into a nucleus at
the caudal end of the medulla, known as the external cuneate nucleus (because it lies just lateral to the
cuneate nucleus, already described). The second-order cells send axons into the cerebellum on the same side
via the cuneocerebellar tract, which—like the dorsal spinocerebellar tract—enters the cerebellum via the
inferior cerebellar peduncle.
The functions of these pathways are:
1. to carry information about the length and tension of muscle fibers in the arms and legs to the cerebellum;
2. to provide information to the cerebral cortex that contributes to a sense of position of the limbs and
digits and of the body in space; i.e., a sense of proprioception (“self-awareness”).
The locations of major components of these pathways are indicated in Figure 4.

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 Mechanosensory pathways

Figure 1. Organization of the central pathways that carry information about discriminative touch, pressure, and
vibration. Information about the body and posterior head is conveyed via the spinal nerves. Information about the
face is conveyed via the fifth cranial nerve. (Illustration by N.B. Cant)

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 Mechanosensory pathways

Gracile
Cuneate fasciculus
fasciculus

Gracile
Gracile nucleus
Cuneate fasciculus
Cuneate
fasciculus
nucleus

Cervical spinal cord

Internal
arcuate
fibers Caudal medulla

Medial
lemniscus

Middle medulla

Figure 2. Dorsal column-medial lemniscus system, with trigeminal lemniscus, in cross-sections. At the level of the
midbrain, the trigeminal lemniscus joins the medial lemniscus so that all mechanosensory information about the
opposite side of the body (including the head) travels together in topographic order as the tracts approach the
thalamus (stick figure in white lines indicates somatotopic order of tracts; second-order neurons are shown in caudal
medulla section). (Sections from Sylvius4 Online) (Figure continued on next page)

4
 Mechanosensory pathways

Medial
lemniscus

Middle pons

Medial
lemniscus

Midbrain

5
 Mechanosensory pathways

Figure 3. Pathways carrying information from the muscle spindles to the cerebellum and to the cerebral cortex.
(Pathways from the dorsal column nuclei to the thalamus and from there to the cortex are shown in a lighter gray.
This part of the pathway was presented in Figure 1.) (Illustration by N.B. Cant)

6
 Mechanosensory pathways

Dorsal nucleus
of Clarke
Dorsal spinocerebellar Dorsal spinocerebellar
tract tract

Thoracic spinal cord Cervical spinal cord Inferior

cerebellar
Dorsal peduncle
spinocerebellar
tract

Caudal medulla
Middle medulla

Inferior
cerebellar
peduncle

Figure 4. Major components

of the pathways conveying
proprioceptive information to
the cerebellum (second-order
Caudal pons
neuron from Clarke’s nucleus
is illustrated in white).
(Sections from Sylvius4
Online)

7
 Mechanosensory pathways
Pathways for light, discriminative touch, pressure, position sense and vibration.
Pathway Receptors First-order Second-order Third-order neurons Primary cortical area Decussation
neurons neurons pattern
dorsal-column medial  encapsulated endings ipsilateral DRGsi ipsilateral dorsal column contralateral ventral contralateral primary somatic sensory caudal medulla: second-
(Meissner’s & Pacinian nuclei in the dorsal, caudal posterior complex of the cortex (S1) in postcentral gyrus order axons of the
lemniscal system (dorsal root ganglion
corpuscles) neurons) medulla: thalamus: Brodmann’s Areas (BA) 3, 1 & 2 dorsal column nuclei
 specialized receptor  gracile nucleus  ventral posterior lateral cross the midline as the
 lower extremity is represented in the internal arcuate fibers
(for postcranial body, systems (Merkel disks) (VPL) nucleus
(Aβ, Ia & II afferent fibers)  cuneate nucleus paracentral lobule and ascend the
including the posterior
(axons of VPL neurons  upper extremity is represented in the brainstem as the medial
portion of the head)
project to the cerebral Ω-shaped segment of the postcentral lemniscus
cortex via the posterior limb gyrus near the middle of the central
[see Figure 9.8A] of internal capsule) sulcus
 light discriminative touch is first
processed in BA 3b
 deep sensation is first processed in BA
3a

trigeminal (principal)  encapsulated endings ipsilateral “DRGs” ipsilateral principal (chief contralateral ventral contralateral S1 pons: second-order
(Meissner’s & Pacinian  trigeminal ganglion sensory) nucleus of the posterior complex of the axons of the principal
mechano-sensory Brodmann’s Areas 3, 1 & 2
corpuscles) neurons in gasserian trigeminal complex in the thalamus: nucleus cross the
system dorsal-lateral pons  face is represented in the inferior midline and ascend the
 specialized receptor (trigeminal) ganglion  ventral posterior medial segment of the postcentral gyrus
systems (Merkel disks) (VPM) nucleus brainstem as the
(for face—anterior third of  light discriminative touch is first trigeminal lemniscus,
(Aβ, Ia & II afferent (axons of VPM neurons processed in BA 3b which occupies a
head) project to the cerebral
fibers)  deep sensation is first processed in BA position near the dorsal
cortex via the posterior limb and medial edge of the
of internal capsule) 3a
[see Figure 9.8B] medial lemniscus
(supplies a face for
lemniscal homunculus)

spino-cerebellar  muscle spindles ipsilateral DRGs ipsilateral relay nuclei in the Ipsilateral cerebellum None! none through the
 Golgi tendon organs thoracic spinal cord and  cortex  no feedforward processing of sensory circuitry of the
(unconscious) (dorsal root ganglion
neurons) caudal medulla: signals in the cerebral cortex via this cerebellum
proprioception  joint receptors  deep nuclei
 dorsal nucleus of Clarke spinocerebellar pathway; this is why it (remember: there is
(for lower extremity) (via the dorsal is considered “unconscious” ipsilateral
(same neurons that send spinocerebellar and representation in the
(for postcranial body,  external cuneate  however, branches of the
branches to the dorsal cuneocerebellar tracts, cerebellum!)
including the posterior nucleus (for upper spinocerebellar axons synapses on
column-medial lemniscal which form the inferior
portion of the head) extremity) proprioceptive dorsal column neurons
pathway) cerebellar peduncle)
[see Figure 9.9] that do send axons into the medial
lemniscus for “conscious”
proprioception

i
The terms ipsilateral and contralateral will refer to the side of the peripheral or central nervous system relative to the location of the sensory receptors; e.g., cortical representation of the somatic sensory periphery occurs in
the contralateral primary somatic sensory cortex.

8
 Pain Systems

Medical Neuroscience | Tutorial Notes

Pain Systems

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.
NCC8. Fundamental discoveries promote healthy living and treatment of disease.

LEARNING OBJECTIVES
After study of today’s learning, the student will:
1. Discuss the complex phenomenology of pain.
2. Describe two categories of pain sensation (first and second pain) and explain the neural basis of each.
3. Characterize the peripheral and central mechanisms underlying hyperalgesia.
4. Characterize the neural mechanisms for the feedback modulation of nociceptive processing.
5. Characterize the neural mechanisms for the feedforward modulation of nociceptive processing.
6. Discuss the affective dimensions of pain and identify the neural systems that are involved in pain affect
(suffering).

TUTORIAL OUTLINE

I. Introduction: complex phenomenology of pain

A. both sensory (nociception) and affective (emotional unpleasantness) dimensions
B. pain usually engages the emotional systems, both in the short-term and the long-term
C. emotional feelings about the long-term consequences of pain, termed secondary affect,
contribute to the psychosocial aspects of pain management
II. Central processing of pain
A. parallel pathways for nociception
1. first order neurons are ganglion cells (DRGs & V-Gs) with peripheral processes that
terminate as free nerve endings (refer back to Figure 9.52 and Table 9.1)
a. primary axons conduct relatively slowly, with most fibers being small and
many ‘unmyelinated’ or only lightly myelinated

1
Visit BrainFacts.org for Neuroscience Core Concepts (©2012 Society for Neuroscience ) that offer fundamental principles about the
brain and nervous system, the most complex living structure known in the universe.
2 th
Figure references to Purves et al., Neuroscience, 5 Ed., Sinauer Assoc., Inc., 2012. [click here]

1
 Pain Systems

b. axons are broadly classified into three groups, which respond to somewhat
different types of painful and/or thermal stimuli
(i) Aδ mechanosensitive nociceptors
- respond to intense or damaging mechanical stimuli
- lightly myelinated; slowly conducting
(ii) Aδ mechanothermal nociceptors
- respond to intense or damaging thermal stimuli
- lightly myelinated; slowly conducting
(iii) C polymodal nociceptors
- respond to thermal, mechanical or chemical stimuli
- unmyelinated; conduct very slowly
c. generally, the receptive fields of nociceptors are relatively large (compared to
innocuous mechanosensory receptors)
d. sensory transduction
i. receptors for nociceptive transduction are members of a large family
of Transient Receptor Potential (TRP) channels
ii. channels are gated by thermal changes, protons (acid), and some
natural compounds (e.g., capsaicin) (see Box 10A)
iii. sensory thresholds can be modified directly and indirectly by
interactions of sensory endings with inflammatory mediators (see
below: peripheral sensitization)
e. central processes of first order neurons enter the dorsal roots and synapse on
local circuit neurons and projection neurons in the superficial dorsal horn
(marginal zone and substantia gelatinosa) and near the base of the dorsal horn
(see Figure 10.3B)
i. as considered below, this local circuitry is important for feedforward
and feedback modulation of nociceptive communication in the CNS
2. there are distinct qualities of pain that are conveyed via parallel central pathways that
originate with these different classes of first order neurons
a. first (sharp) pain
i. early perception of “sharp” pain conveyed by Aδ afferent fibers (see
Figure 10.2)
ii. relayed via the ventral posterior complex of the thalamus to S1, both
of which are somatotopically organized
iii. provides information about acute onset of pain and location of injury
- provides input to segmental spinal reflexes that withdraw limb
from painful stimuli
- provides warning of tissue damage and encourages escape
from source of injury

2
 Pain Systems

b. second pain
i. later, longer-lasting perception of a “dull”, burning type of pain
conveyed by C fibers (see Figure 10.2)
ii. relayed to widespread cortical areas via other thalamic and brainstem
projections, with little somatotopic organization
iii. provides information about ongoing presence of trauma, with little
specification of the location of injured tissues
- may encourage ‘guarding’ or disuse of injured region (e.g.,
promote modified gait to avoid weight-bearing)
- provides input to ‘limbic’ structures in the medial and ventral
forebrain that process the affective dimensions of pain
B. affective dimensions of pain (see Figure 10.5)
1. nociceptive signals reach ‘limbic’ structures in the forebrain, including the anterior
cingulate gyrus, insular cortex, amygdala and orbital-medial prefrontal cortex
a. subcortical inputs arise from brainstem centers and several thalamic nuclei
(outside of the ventral posterior complex)
b. cortico-cortical inputs arise from higher-order somatic sensory areas in the
parietal lobe
2. nociceptive sensations become integrated together with the other somatic and
visceral sensations arising from changes in body state (related to alterations in
autonomic and somatic motor activity) and cognitive processes, all of which gives rise
to the subjective feelings associated with pain
3. ongoing appraisals of these complex somatic and visceral sensations and their long-
term consequences gives rise to secondary affect

III. Visceral Pain

A. visceral pain pathways: conveyed up the neuraxis via a newly discovered pathway in the
dorsal columns of the spinal cord (see Table above)
B. referred pain (see Box 10B)
1. some primary afferents from the viscera synapse on second order neurons in the
dorsal horn that also receive input from more superficial (non-visceral) nociceptors
2. consequently, activation of visceral nociceptors may lead to visceral pain percepts and
percepts associated with peripheral cutaneous fields, a phenomenon known as
“referred pain”
3. convergence may also occur at other gray matter centers along the somatic sensory
pathways (e.g., dorsal column nuclei)

IV. Hyperalgesia (inflammatory pain)

A. enhanced sensitivity to mechanosensory stimulation in a local region surrounding an area of
tissue damage

3
 Pain Systems

B. due to peripheral sensitization of nociceptors by paracrine mediators of inflammation (see

Figure 10.7)
1. mediate immune response to injury and increase in local perfusion of damaged tissues
2. increase the sensitivity of nearby nociceptors by directly altering sensory transduction
at the TRP receptors
3. activate second messenger systems within the terminal endings of the nociceptors
4. release of neuropeptides by the nociceptor ending itself, which in turn, facilitate the
local inflammatory response
5. these diverse mechanisms are potential targets for pharmaceutical intervention (e.g.,
aspirin inhibits synthesis of prostaglandins)
C. central sensitization may also contribute to hyperalgesia
1. activity-dependent increase in the excitability of second-order neurons (dorsal horn)
following high levels of nociceptor activity
2. may generalize to other sources of input to second-order neurons
a. some primary nociceptive afferents synapse on second order neurons in the
dorsal horn that also receive input from mechanosensory afferents
b. should such second-order neurons become sensitized, an innocuous input may
become painful (= allodynia)
3. two mechanisms of central sensitization (a form of LTP):
a. transcription independent (“wind-up”)
i. repeated activation of nociceptors leads to a sustained depolarization
of the second–order neuron
ii. postsynaptic conductances gated by glutamate become more effective
in depolarizing neurons
b. transcription dependent
i. activation of second messenger systems may lead to changes in gene
transcription that increase the excitability of the second-order neuron
V. Central Regulation of Nociception and Pain
A. analgesia: the absence of pain in the presence of a nociceptive stimulus
B. the perception of pain is subject to a broad range of modulatory influences
1. contextual influences
a. emotional context of trauma (e.g., stress) can heighten or diminish sensations
of pain
b. cognitive understanding (“expectation”) can similarly shape the experience of
pain (e.g., the placebo effect, exercise)
c. cultural differences in a person’s response to painful stimuli
d. at least some of these influences may be explained by “descending” neural
pathways that modulate the central transmission of nociceptive information
2. feedback (descending) modulation of nociception

4
 Pain Systems

a. higher centers, including the somatic sensory cortex, the limbic forebrain and
hypothalamus, project to groups of neurons in the brainstem that modulate
that primary transmission of nociceptive signals (see Figure 10.8A)
i. descending projections from the telencephalon target (among many
sites) the periaqueductal gray of the midbrain
ii. these midbrain structures in turn project to serotonergic neurons in
the pontine Raphe nuclei, noradrenergic neurons in the locus
coeruleus (pons), and portions of the reticular formation in the
ventral lateral medulla
iii. neurons in these brainstem regions project to the dorsal horn of the
spinal cord and the spinal trigeminal nucleus
iv. some of these neurons release a wide variety of excitatory and
inhibitory neurotransmitters, including biogenic amines (serotonin,
norepinephrine), that can activate local circuit neurons in the dorsal
horn that release opioids (endorphins, enkephalins, dynorphins)
v. the analgesic effects of opioids in the dorsal horn are due to the
interruption of nociception at the first synapse in the pathway
vi. opioids also have more widespread analgesic actions by modulating
descending systems, as well as cortical neurons that generate painful
perceptions (opioid receptors are widespread in the CNS)
vii. perhaps the placebo effect (an other related phenomena that
manipulate “expectation”) is mediated by endogenous opioids acting
upon this descending modulatory system
3. feedforward modulation of nociception: “gate theory” of pain
a. central idea: pain results from the balance of activity in nociceptive and non-
nociceptive afferents
b. activation of non-nociceptive inputs inhibits firing of second-order neurons by
activating an inhibitory interneuron (see Figure 10.8B)
c. non-nociceptive inputs ‘close’ the gate and prevent pain transmission

VI. Chronic Pain

1. nociceptive chronic pain
a. results from ongoing stimulation of nociceptors
b. involves both first and second pain
2. chronic pain syndromes
a. typically, chronic pain with no known nociceptive etiology
b. common examples: chronic lower back pain, fibromyalgia
c. etiology remains poorly defined
d. recent proposals include dysregulation of descending modulatory systems
(e.g., diminished input to periaqueductal gray)

5
 Pain Systems

VII. Neuropathic Pain

A. results from abnormal patterns of activity in nociceptive pathway unrelated to the
presence of a noxious stimulus in the periphery
B. peripheral causes (e.g., nerve compression, inflammation)
C. accompanied by abnormal somatic sensations
D. may involve abnormal activity in sympathetic nervous system
E. may have central nervous system causes
1. sustained sensitization of neurons in the nociceptive pathway
2. plasticity at higher levels of somatic sensory and motor representation (e.g.,
phantom limb pain; see Box 10D)

6
 Pain  Pathways  •  Spring  2013  

Medical  Neuroscience  |  Tutorial  

Pain  Pathways  

MAP  TO  NEUROSCIENCE  CORE  CONCEPTS1  

NCC1.   The  brain  is  the  body's  most  complex  organ.  
NCC3.   Genetically  determined  circuits  are  the  foundation  of  the  nervous  system.  
NCC7.   The  human  brain  endows  us  with  a  natural  curiosity  to  understand  how  the  world  works.  
NCC8.   Fundamental  discoveries  promote  healthy  living  and  treatment  of  disease.  

LEARNING  OBJECTIVES  
After  study  of  today’s  learning,  the  student  will:  
1. Characterize  the  organization  of  the  anterolateral  system  from  peripheral  nerve  ending  to  cerebral  
cortex.  
2. Recognize  components  of  the  anterolateral  system  in  the  spinal  cord,  brainstem,  thalamus  and  
cerebral  cortex.2  
3. Characterize  the  organization  of  the  trigeminal  pain  &  temperature  (spinal  trigeminal)  system  from  
peripheral  nerve  ending  to  cerebral  cortex.  
4. Recognize  components  of  the  trigeminal  pain  &  temperature  (spinal  trigeminal)  system  in  the  
brainstem,  thalamus  and  cerebral  cortex.1  

TUTORIAL  NARRATIVE  

Introduction  
There  are  two  major,  parallel  systems  that  convey  somatic  sensory  information  from  the  periphery  of  the  post-­‐
cranial  body  to  the  cortex,  the  dorsal  column-­‐medial  lemniscus  system  and  the  anterolateral  system.  There  
are  comparable  parallel  systems  carrying  information  from  the  face  associated  with  the  central  projections  of  
the  trigeminal  nerve.  In  addition,  there  is  an  important  system  carrying  proprioceptive  information  from  the  
muscle   spindles   to   the   cerebellum.   This   tutorial   will   focus   on   the   pathways   taken   by   the   components   of   the  
systems   for   transmission   of   neural   signals   pertaining   to   pain   and   temperature   sensation.   It   is   important   for  
your  understanding  of  neurological  deficits  seen  in  the  clinic  to  know  where  these  pathways  travel  relative  to  
each  other  and  to  other  structures  (including  the  cranial  nerve  nuclei)  in  the  brain.  
 

   

1
  Visit  BrainFacts.org  for  Neuroscience  Core  Concepts  (©2012  Society  for  Neuroscience  )  that  offer  fundamental  principles  about  the  
brain  and  nervous  system,  the  most  complex  living  structure  known  in  the  universe.  
2
  As  you  study  somatic  sensory  pathways,  you  should  begin  referring  to  cross  sections  through  the  nervous  system  (e.g.,  in  Sylvius4)  so  
that  you  can  recognize  where  relevant  nuclei  and  axonal  tracts  are  located  within  the  brain  and  spinal  cord.  

1
 Pain  Pathways  •  Spring  2013  

Pathways  mediating  pain  and  temperature  sensation.  

The  anterolateral  system  is  responsible  for  conveying  information  about  pain,  temperature  and  crude  touch  
(i.e.,   touch   lacking   the   spatial   resolution   of   the   dorsal   column   system)   from   the   post-­‐cranial   body.   Comparable  
information   about   the   face   is   processed   in   trigeminal   pathways.   These   pathways   are   illustrated   in   Figures   1  
and  2.  Most  peripheral  processes  associated  with  the  dorsal  root  ganglion  cells  that  contribute  to  this  system  
are  “free.”  That  is,  they  are  not  associated  with  encapsulated  endings  like  those  in  the  dorsal  column-­‐medial  
lemniscal   system.   In   addition,   the   first-­‐order   fibers   associated   with   the   anterolateral   system   are   generally  
much   smaller   in   diameter   than   those   associated   with   the   dorsal   column   system.   (So   what   does   this   tell   you  
about  the  relative  conduction  velocities  of  these  two  important  somatic  sensory  pathways?)  
The  first-­‐order  neurons  in  the  anterolateral  system,  like  those  in  the  dorsal  column-­‐medial  lemniscal  system,  
have  their  cell  bodies  in  the  dorsal  root  ganglia.  The  central  processes  of  these  neurons   terminate  on  second-­‐
order  neurons  in  the  dorsal  horn  of  the  spinal  cord.  Pain  and  temperature  information  from  receptors  in  the  
face   is   carried   into   the   brain   on   the   fifth   nerve.   The   cell   bodies   of   the   first   order   neurons   are   in   the  trigeminal  
ganglion   and   the   central   processes   of   the   cells   make   synapses   in   a   nucleus   in   the   medulla   known   as   the  spinal  
trigeminal   nucleus  (of  the   fifth   nerve).   This   nucleus   is   actually   continuous   with   the   dorsal   horn   of   the   spinal  
cord.  
The  second-­‐order  neurons  in  the  dorsal  horn  of  the  spinal  cord  send  their  axons  across  the  midline,  where  they  
accumulate  in  the  anterolateral  (ventrolateral)  part  of  the  white  matter.  They  ascend  in  this  location  through  
the   length   of   the   cord.   Many   of   these   fibers   continue   through   the   medulla,   the   pons   and   the   midbrain   to  
contact   third-­‐order   neurons   in   the   ventral   posterior   lateral   (VPL)   nucleus   of   the   thalamus   (as   well   as   other  
thalamic   nuclei).   This   direct   pathway   from   the   spinal   cord   to   the   thalamus   is   often   called   the   spinothalamic  
tract.  Actually,  the  thalamus  is  only  one  of  the  targets  of  the  second-­‐order  neurons  in  the  anterolateral  system.  
These   neurons   also   project   to   central   parts   of   the   medulla,   pons   and   midbrain   known   collectively   as   the  
reticular  formation  (this  component  of  the  anterolateral  system  is  known  as  the  “spinoreticular  tract”)  and  to  
the   periaqueductal   gray   matter   and   the   superior   colliculus   (this   component   is   known   as   the  
“spinomesencephalic  tract”).  Second-­‐order  neurons  located  in  the  spinal  trigeminal  nucleus  send  their  axons  
across  the  midline  to  form  the  ventral  trigeminothalamic  tract,  which  travels  to  the  ventral  posterior  medial  
(VPM)  nucleus  of  the  thalamus.  
Third-­‐order  neurons  in  the  ventral  posterior  nucleus  and  in  other  thalamic  nuclei  then  project  to  the  cortex  via  
the   internal   capsule.   The   postcentral   gyrus   appears   to   be   important   for   the   ability   to   discriminate   the   exact  
location  of  painful  stimuli,  but  many  other,  less  well-­‐understood  cortical  areas  (including  areas  in  the  anterior  
part  of  the  cingulate  gyrus)  appear  to  be  important  in  the  complete  sensation  of  pain,  including  the  complex  
affective  dimensions  of  pain.  
Figure   3   presents   a   diagram   of   the   major   parallel   pathways   carrying   somatic   sensory   information   to   the  
cerebral  cortex  (see  tutorial  notes  on  “Mechanosensory  Pathways”).  The  pathways  for  mechanoreception  
and  the  pathways  for  pain  and  temperature  sensation  shown  in  Figure  A1  are  shown  together  bilaterally.  
 
   

2
 Pain  Pathways  •  Spring  2013  

 
 

 
Figure  1.  Organization  of  the  central  pathways  for  pain  and  temperature  sensation.  These  pathways  also  carry  crude  
information  about  touch.  (As  discussed  an  earlier  tutorial,  there  is  a  small  input  into  the  trigeminal  nuclei  from  the  
seventh,  ninth  and  tenth  nerves,  but  this  input  is  of  little  significance  clinically.)  (Illustration  by  N.B.  Cant)  
   

3
 Pain  Pathways  •  Spring  2013  

 
 
 
Spinal   Spinal  
  Dorsal   trigeminal   trigeminal  
horn   tract   nucleus  
 
 
 
 
 
Anterolateral  
  Cervical  spinal  cord   system   Anterolateral  
  system  

  Caudal  medulla  

 
 
 
 
Spinal  
Region  of  ventral   Spinal  
  trigeminal  
trigeminothalamic   trigeminal  
tract  
  tract   nucleus  

 
 
 
 
Anterolateral  
  system
 
 
 
  Middle  medulla  
 
 
Figure   2.   Location   of   the   anterolateral   system   in   the   cervical   cord   and   brainstem,   with   the   ventral  
trigeminothalamic  tract,  as  seen  in  cross-­‐sections.  Note  that  at  all  levels,  the  fibers  of  both  tracts  are  located  in  
the  anterolateral  part  of  the  brainstem  tegmentum  (second-­‐order  neurons  are  illustrated  in  white).  (Sections  
from  Sylvius4)  (Figure  continued  on  next  page)  
   

4
 Pain  Pathways  •  Spring  2013  

 
 
Spinal  trigeminal  
nucleus  &  tract  
Region  of  ventral  
trigeminothalamic  tract  

Anterolateral  
system  

Caudal  pons  
 
 
 
 
Region  of  ventral  
  trigeminothalamic  tract  

Midbrain   Anterolateral  
system  

 
 
   

5
 Pain  Pathways  •  Spring  2013  

 
 
Figure  3.  A  diagram  of  the  major  parallel  pathways  carrying  somatic  sensory  information  to  the  cerebral  cortex.  
The  pathways  for  mechanoreception  and  the  pathways  for  pain  and  temperature  sensation  are  shown  together  
bilaterally  in  this  figure.  See  related  figures  labels  of  nuclei  and  tracts.  (Illustration  by  N.B.  Cant)  
 

6
 The Eye

Medical Neuroscience | Tutorial Notes

Visual System: The Eye

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the factors and neural mechanisms that account for the focusing of an image on the
retina.
2. Identify the five neuronal cell types of the retina and state the roles of each in retinal
processing.
3. Characterize the molecular processes that underlie phototransduction.
4. Discuss the responses of retinal ganglion cells to the onset and offset of light and the relevance
their receptive fields for the detection of light and shadow.

TUTORIAL OUTLINE

I. Review the gross anatomy of the human eye (see Figure 11.12)

II. Formation of optical images

A. refraction: “bending” of light that occurs at the interface of different optical media
1. most (~80%) of refraction occurs as light passes through the cornea
2. sharp focusing of images at variable distances from the eye requires an
adjustable lens, by a process called accommodation
B. accommodation
1. dynamic changes in the refractive power of the lens
a. when the lens is flat … least refractive power (far vision)
b. when lens is rounded … most refractive power (near vision)
2. control of lens shape (see Figure 11.2)

1
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 The Eye

a. lens is an elastic structure that tends to round up

b. the lens is attached to the circular ciliary muscle by an array of zonule
fibers; the resting tension exerted by the zonule fibers is sufficient to
pull the lens into a flattened position
c. to focus on a near object, the lens must become more rounded, which is
accomplished by the contraction of the ciliary muscle
(i) contraction of the circular ciliary muscle brings the attachment
points of the zonule fibers closer to the lens
(ii) this relieves tension on the lens and the lens’s intrinsic elasticity
allows it to round up
3. adjustments of pupil size also contribute to focusing of images on the retina
a. because optical aberrations are greatest as light passes through the
edges of the lens, the pupil minimizes these errors by restricting the
passage of light to the center of the lens
b. a very small pupil severely limits the amount of light entering the eye,
which may be detrimental under conditions of dim illumination
c. the neural control over pupil size (see Figure 12.2) provides for a
optimization of these two competing considerations under varying
conditions of illumination

III. Inner layer of the eye

A. comprises two tissues derived from the developing diencephalon (see Figure 11.4)
1. neural retina (see below)
2. pigment epithelium (see Figure 11.6)
a. tissue containing the pigment, melanin (albino individuals lack this
pigment and are highly “light sensitive”)
b. reduces the back scattering of light
c. absorbs photoreceptor disk membrane and recycles photopigment
d. photoreceptors become dysfunctional and eventually nonfunctional if
separated from the pigmented epithelium (e.g., retinal detachment)
B. basic wiring diagram of the retina (see Figure Figure 11.5)
1. five neuronal cell types stacked into five histological layers of alternating cell
bodies and neuropil (cellular processes and synapses)
a. direct flow of information mediated by a three-neuron chain:
(i) photoreceptors: main sensory transducers in retina; two basic
types: rods and cones (generate graded potentials)
(ii) bipolar cells: interneurons between photoreceptor and
ganglion cells (generate graded potentials)

2
 The Eye

(iii) ganglion cells: integrates electrical activity from bipolar (and

amacrine) cells and gives rise to axons that form the optic
nerve; only cell class in retina that fires action potentials
b. lateral interactions mediated by two cell types:
(i) horizontal cells: mediate lateral interactions between
photoreceptors and bipolar cells
(ii) amacrine cells: mediate lateral interactions between bipolar
cells, other amacrine cells and ganglion cells
2. in addition, there is specialized type of glial cell (called the Müller cell) that helps
to maintain the ionic environment across the retina
3. light path: through the retinal layers!

IV. Phototransduction
A. in the dark, photoreceptors are depolarized (to about -40 mV) and are continuously
releasing their neurotransmitter, which is glutamate
1. cation-selective ion channels in the outer segments of the photoreceptors are
gated by cytoplasmic cGMP (see Figure 11.8)
2. in the dark, cGMP levels are high and cations flow into the outer segments
(called the “dark current”), keeping the cell in a depolarized state
B. effects of light
1. photopigments
a. in the membranous disks of the outer segments there are a variety of
photopigment molecules that consist of two subunits:
(i) a light-absorbing component, 11-cis retinal
(ii) any one of a number of opsin proteins that fine-tune the
molecular absorption of 11-cis retinal
b. the best known photopigment is rhodopsin, the pigment of rods
c. cones have one of three photopigments that are sensitive to short,
medium or long wavelengths of light (see Figure 11.14)
2. when light strikes the outer segments, photoreceptors hyperpolarize (to about -
65 mV) and release much less glutamate (see Figure 11.8-11.10)
a. absorption of a photon of light by rhodopsin leads to a conformation
change and the activation of a G-protein, called transducin
b. transducin activates a phosphodiesterase that hydrolyzes cGMP
c. cGMP concentrations in the outer segment fall and the cation-selective
channels close, which leads to hyperpolarization
3. amplification: this complex second messenger cascade allows for great
amplification of the initial event

3
 The Eye

V. Rods and Cones (see Figure 11.11-11.13)

A. rods: very low spatial resolution, but extremely sensitive to light
1. large outer segments in a rod-like shape maximizes the amount of
photopigment that can be contained and made available for transduction
2. greater molecular amplification in transduction cascade; sensitive to 1 photon
(cones typically require about 100 photons to become activated)
3. predominant type of photoreceptor across the retina, except for the fovea
4. convergence pattern: the ratio of rods to ganglion cells is relatively high (signals
derived from many rods converge onto the same ganglion cell)
B. cones: very high spatial resolution, but relatively insensitive to light
1. different cones with different absorption spectra make color vision possible
2. convergence pattern: the ratio of cones to ganglion cells is very low,
approaching 1 to 1 in the fovea (= “pit”), a specialized part of the retina where
cones are very dense and visual acuity is greatest
C. rods and cones make different contributions to visual activity
1. scotopic vision: very low levels of illumination when only rods are activated
2. mesopic vision: low levels of illumination (e.g., under moonlight) when both
rods and cones are activated
3. photopic vision: moderate and high levels of illumination when rods are
saturated and only cones are activated
VI. Ganglion cell receptive fields
A. receptive field (in the visual system): region of visual space (or region of the retina) that
when illuminated or darkened elicits a response in a visual sensory neuron
B. center-surround structure of ganglion cell receptive fields (see Figure 11.17)
1. center: small circular region
a. ON center: ganglion cell increases its firing rate when light falls on the
center of the its receptive field
b. OFF center: ganglion cell decreases its firing rate when light falls on the
center of its receptive field
2. surround: larger annulus surrounding the receptive field center
a. surround antagonizes the center
(i) ON center cells have OFF surrounds
(ii) OFF center cells have ON surrounds
c. OFF surround: firing rate decreases when light falls on the surround
d. ON surround: firing rate increases when light falls on the surround
3. center/surround design allows for increased sensitivity to luminance contrast,
such as the edge of shadow (see Figure 11.19)

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 The Eye

C. retinal circuitry underlying ganglion cell receptive fields

1. receptive field structure is generated in the outer plexiform layer, by the
interactions of photoreceptors, bipolar cells and horizontal cells
2. two physiological classes of bipolar cells define the center response type of
ganglion cells (see Figure 11.18)
a. ON center bipolar cells hyperpolarize in response to the glutamate
released by photoreceptors, due to the activation of metabotropic
receptors and their related second-messenger systems
b. OFF center bipolar cells depolarize in response to glutamate released by
photoreceptors, due to activation of AMPA receptors
c. bipolar cells respond with graded potentials, not action potentials
(i) they release more neurotransmitter when depolarized
(ii) they release less neurotransmitter when hyperpolarized
So now consider what happens when light strikes the center of a ganglion cell’s receptive
field center. Be prepared to explain why ON-center ganglion cells increase their activity and
OFF-center ganglion cells decrease their activity in terms of the neurophysiology of bipolar
cells in the middle of the retina.

3. lateral interactions mediated by horizontal cells account for center-surround

antagonism

LEARNING OBJECTIVES
Q1. In order to properly fixate nearby, stationary visual targets and focus their images on the retina,
each of the following actions listed below usually occurs, EXCEPT for one. Identify the action
that IS NOT part of the normal response to visual fixation.
A. the shape of the lens in each eye is altered
B. vergence eye movements (convergence or divergence)
C. the firing rate of brainstem neurons that govern iris constrictor muscles is altered
D. the shape of the cornea in each eye is altered
E. the diameter of the pupils is altered

Q2. Which of the following natural stimulus configurations provides the BEST stimulus for an OFF-
center ganglion cell?
A. uniform illumination across the entire receptive field
B. the edge of a shadow that falls across the border between the center and surround of
the receptive field, with the center region in shadow
C. a small spot of light that falls within the surround region
D. the edge of a shadow that falls across the border between the center and surround of
the receptive field, with the center region illuminated
E. uniform shadow across the entire receptive field

5
 Central Visual Processing

Medical Neuroscience | Tutorial Notes

Visual System: Central Visual Processing

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the distribution of the axons of retinal ganglion cells to major processing centers in the
forebrain and brainstem.
2. Discuss the major receptive field properties of V1 neurons.
3. Discuss the functions of parietal and temporal “extrastriate” visual pathways.

TUTORIAL OUTLINE

I. Functional organization of V1
A. the primary visual cortex (V1) is also known as the “striate cortex”
1. “striate” because of a prominent band of white matter (stria of Genari) that
runs through the middle of cortical layer 4, giving this region of the cortex a
distinctive appearance
2. Brodmann recognized this cortical region as Area 17
B. neurons in V1 show response properties that are not elaborated at previous stages of
neural processing (some of the best examples of “computational” functions of the
cerebral cortex are known from neurophysiology studies of V1)
C. receptive field properties of cortical neurons in V1
1. V1 neurons respond best to moving edges of light and shadow
a. small spots of light that evoke vigorous discharges in retinal ganglion
cells and LGN neurons are not very effective in driving V1 neurons
b. V1 neurons respond best to a moving edge that is within a narrow range
of orientations in space (e.g., horizontal, vertical, oblique); this property
is known as orientation selectivity (see Figures 12.8, 12.10 & 12.122)

1
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1
 Central Visual Processing

c. many V1 neurons respond best when a particular orientation moves in

only one direction (e.g., a vertical edge moving from right to left); this
property is known as direction selectivity
2. ocularity
a. the retinal inputs to the LGN terminate in separate layers, so that
individual neurons in the LGN are monocular
b. the projections of these monocular LGN neurons to layer 4 of V1 remain
segregated within layer 4 (see Figure 12.13)
(i) LGN afferents terminate in alternating bands or columns in layer
4, called ocular dominance columns
(ii) monocular neurons in the ocular dominance columns of layer 4
converge onto neurons in layers 2 and 3, where binocularity is
first established in the visual pathway
3. stereopsis
a. because neurons in V1 (after layer 4) are binocular, neural signals are
generated that take advantage of the fact that, for near objects, the
lines of sight of the two eyes are slightly different (see Figure 12.14)
b. for all objects near or far from the plane of fixation, images of the
objects fall on “non-corresponding” locations in the two retinas
c. many cells in V1 (and in other visual cortical areas) are sensitive to such
retinal disparities
d. these neural signals are the basis of stereopsis, which provides one
important cue about the location of objects in depth (this
computational property in V1 is necessary for the 3D effect in visual
media!)
e. other cues about depth include motion parallax and size constancy
D. parallel pathways
1. there are distinct anatomical and physiological classes of retinal ganglion cells,
each of which is organized into ON and OFF center-surround subtypes
2. three important classes are the M, P and K ganglion cells (see Figure 12.15)
a. M ganglion cells have larger cell bodies, dendritic arbors and axons
compared to P cells; thus, M cells have larger receptive fields and their
axons conduct faster than P cells
b. M cells respond transiently (phasically) to visual stimuli, while P cells
show a more sustained (tonic) response
c. P cells are sensitive to color, while M cells are “color-blind”
(i) receptive field centers and surrounds of P cells are driven by
different types of cones (e.g., red and green)

2 th
Figure references to Purves et al., Neuroscience, 5 Ed., Sinauer Assoc., Inc., 2012. [click here]

2
 Central Visual Processing

(ii) P cells respond best to differences in color striking their centers

and surrounds (e.g., red center and green surround)
(iii) the centers and surrounds of M cells are both driven by
different types of cones
3. M and P ganglion cells terminate in different sets of layers in the LGN, the
magnocellular (“large cell”) layers (layers 1 and 2) and parvocellular (“small
cell”) layers (layers 3-6), respectively
4. In V1, the inputs from magnocellular and parvocellular LGN neurons are partially
segregated into functional “streams” of processing, a magnocellular stream for
detecting quickly moving stimuli and a parvocellular stream for detailed
examination of form (acuity) and color (see below)
5. there are also K ganglion cells that project to small clusters of “konio” cells that
reside between the major laminae of the LGN; this so-called koniocellular
pathway is conveyed to V1 in projections that terminate in patches in layer 2/3
(an exception to the thalamus-to-layer 4 rule)
VIII. Extrastriate Visual Cortex
A. beyond V1 (= “striate cortex”), there are multiple areas in the occipital, parietal and
temporal lobes that process visual information (see Figure 12.16-12.18)
B. these areas are arranged into two broad functional pathways that feed visual
information from V1 into associational cortical areas in the parietal and temporal lobes
(see Figure 12.18):
1. dorsal or lateral parietal pathway: responsible for spatial aspects of vision, such
as the relationships between objects and ourselves and the movements of
objects (including ourselves) through the environment (i.e., “where?”)
2. ventral or inferior temporal pathway: responsible for high-resolution form
vision, color processing and object recognition (i.e., “what?”)
C. although both pathways receive input from both parvocellular and magnocellular
streams in V1, there tends to be more ‘magnocellular’ influence on the parietal pathway
and more ‘parvocellular’ influence on the temporal pathway
D. damage to cortical areas in the parietal and temporal pathways produce different visual
deficits, such as the selective loss of color vision or an inability to recognize a familiar
face (ventral temporal pathway), or the loss of motion perception (parietal pathway,
involving lesions in visual areas MT/MST in particular)

3
 Central Visual Processing

STUDY QUESTION
The primary visual cortex (V1) performs a number of important functions in visual encoding and visual
perception. However, which of the following functions is best attributable to higher-order visual cortical
areas beyond V1?
A. the recognition and identification of complex visual stimuli, such as human faces
B. provision of neural input to the parietal and temporal visual processing streams
C. binocular vision; i.e., bringing together in a binocular pathway the neural signals derived
from the two eyes
D. stereopsis; i.e., computations about depth based on slight differences in the views of
the two eyes
E. the analysis of simple elements of visual stimuli, such as the orientation of contours,
their direction of motion, and their location in visual space

4
 Central Visual Pathways

Medical Neuroscience | Tutorial Notes

Visual System: Central Visual Pathways

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the distribution of the axons of retinal ganglion cells to major processing centers in the
forebrain and brainstem.
2. Discuss the topographic representation of visual space in the primary visual cortex (V1) and its
anatomical basis in the organization of visual projections.
3. Discuss the distribution and functions of parietal and temporal “extrastriate” visual pathways.

TUTORIAL OUTLINE

I. Overview of Central Visual Pathways

A. central projections of the retina arise from retinal ganglion cells
B. projections terminate on a variety of structures in the diencephalon and midbrain (see
Figure 12.12 for gross overview)
1. diencephalic targets
a. dorsal lateral geniculate nucleus (LGN)
(i) principal target of retinal ganglion cells
(ii) relays visual signals to the primary visual cortex (V1)
(iii) this pathway, is responsible for most aspects of what we know
as visual perception
b. suprachiasmatic nucleus of the hypothalamus
(i) responsible for entraining endogenous circadian (daily) rhythms
to natural day-night cycle

1
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1
 Central Visual Pathways

(ii) the light-sensing elements in this visual projection are a special

class of photosensitive ganglion cells that contain another
photopigment, melanopsin
2. midbrain targets
a. superior colliculus
(i) involved in coordinating orienting movements of the head and
eyes to a visual stimulus (and other sensory stimuli)
b. pretectum
(i) involved in pupillary light reflex (see Figure 12.2)
See tutorial on “Visual System – Pupillary Light Reflex”.
Be sure that you know the neuroanatomical basis of the pupillary light
reflex and what can be learned about the integrity of the nervous system
as you consider the possible outcomes of this test (e.g., constriction of the
left eye, but not the right eye, when light is presented to the right eye,
vice versa, etc.)

(ii) pretectum is also involved in coordinating the activities of the

preganglionic neurons that innervate the ciliary muscles and
allow for accommodation
C. parallel processing in visual pathways begins with distinct anatomical and physiological
classes of retinal ganglion cells and continues into the array of cortical areas that
process different aspects of visual information

II. The pathway from the retina to V1 in more detail

A. from retina to brain (see Figure 12.1)
1. ganglion cell axons leave the retina at the optic disk and project centrally in the
optic nerve (“CN” II—not really a nerve, but an extension of the brain)
2. about 55% of the optic nerve axons cross the midline (i.e., decussate) in the
optic chiasm and project to the contralateral hemisphere; the other 45% remain
ipsilateral (see below for consideration of retinotopy)
3. central to the optic chiasm, ganglion cell axons form the optic tract, which is
simply the central continuation of optic chiasm
4. axons (and branches of axons) exit the optic tract and terminate in central
targets in the diencephalon and/or midbrain
5. the principle projection to the visual parts of the cerebral cortex originates in
the LGN and terminates in V1, Brodmann’s Area 17 (also called the “striate
cortex”, for its prominent striation in the human brain), which is located in the
banks of the calcarine fissure on the medial aspect of the occipital lobe
B. retinotopic organization of the visual field projections
1. general principles

2
 Central Visual Pathways

a. the nearest neighbor relationships within each half-retina are

maintained throughout the projections to the LGN and primary visual
cortex; this is termed “visuotopy” or “visual topography”
b. however, each hemisphere (LGN and V1) represents the CONTRALATERAL
visual hemifield
2. anatomical basis in the retina for visuotopy
a. some important conventions (see Figure 12.3A)
a. the point of fixation is in the center of the visual field
b. the vertical meridian projects as a vertical line that passes
through the fovea of each retina
c. similarly, the horizontal meridian projects as a horizontal line
that also passes through the fovea
d. temporal refers to the half of the retina (or visual space) that is
lateral to the fovea (or vertical meridian)
e. nasal refers to the half of the retina (or visual space) that is
medial to the fovea (near the vertical meridian)
b. each retina sees overlapping regions of visual space that includes
portions of both visual hemifields (see Figure 12.3B)
(i) binocular visual field is seen by nasal and temporal parts of
both retinas
(ii) monocular crescents of visual space (far temporal in visual
space) are seen only by the extreme medial portion of the nasal
retina (the nose gets in the way!)
c. the lens inverts and reverses the optical image: the superior part of the
visual field is seen by the inferior part of the retina, and the temporal
half of the visual field is seen by the nasal half of the retina
d. how are the central projections from “corresponding” points in each
retina that see the same position in visual space brought together in the
brain? (see Figure 12.4)
a. axons of ganglion cells in the nasal retina decussate in the optic
chiasm and project to the contralateral hemisphere
b. the axons of ganglion cells in the temporal retina do not cross
and remain ipsilateral
c. the line of decussation in the retina runs through the fovea
3. in the LGN
a. each optic tract terminates in an orderly fashion, so that each LGN
contains an orderly map of the contralateral visual hemifield
b. however, the axons from each retina terminate in distinct layers
4. in V1

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 Central Visual Pathways

a. the projections of the LGN to V1 terminate in proper topographic order

in cortical layer 4 (see Figure 12.5)
b. the fovea is represented in the posterior part of the calcarine sulcus,
with more peripheral parts of the contralateral visual hemifield
represented in progressively more anterior locations
c. the upper visual field is represented in the inferior bank of the calcarine
sulcus, while the lower visual field is represented in its superior bank
d. the representation of the fovea is disproportionately large (like the
“over-representation” of the hand in S1)
e. on the way to V1, the projection of the LGN is called the optic radiation
(see Figure 12.7)
(i) the lateral-inferior part, called Meyer’s loop, “loops” into the
white matter of the temporal lobe before projecting onto the
inferior bank of the calcarine sulcus (terminating in the lingual
gyrus)
(ii) the more medial-superior fibers course through the white
matter of the parietal lobe before projecting onto the superior
bank of the calcarine sulcus (terminating in the cuneus gyrus)
III. Extrastriate Visual Cortex
A. beyond V1 (= “striate cortex”), there are multiple areas in the occipital, parietal and
temporal lobes that process visual information (see Figure 12.16-12.18)
B. these areas are arranged into two broad functional pathways that feed visual
information from V1 into associational cortical areas in the parietal and temporal lobes
(see Figure 12.18):
1. dorsal or lateral parietal pathway: responsible for spatial aspects of vision, such
as the relationships between objects and ourselves and the movements of
objects (including ourselves) through the environment (i.e., “where?”)
2. ventral or inferior temporal pathway: responsible for high-resolution form
vision, color processing and object recognition (i.e., “what?”)

4
 Central Visual Pathways

STUDY QUESTIONS
Q1. Where are the cell bodies that grew their axons into the right optic tract?
A. left nasal retina
B. right nasal retina
C. left temporal retina
D. right temporal retina
E. A&D
F. B&C
G. A&B
H. C&D

Q2. There is a female patient who happens to enjoy a hot cup of tea most days at about 4:00 PM.
Her problem is that she frequently spills her tea. The reason she spills her tea is that she does
not appreciate the movement of tea filling her tea cup as she pours it out. She also has great
difficulty judging the movement of traffic when she crosses a street at a crosswalk. Which of the
following best explains her visual impairment?
A. She is blind in her non-dominant eye.
B. She is blind in her dominant eye.
C. She has torn the center of her optic chiasm.
D. She has a lesion in her inferior occipitotemporal association cortex in her non-dominant
hemisphere.
E. She has a lesion in her lateral parieto-occipital associational cortex in her dominant
hemisphere.

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 Visual Field Deficits

Medical Neuroscience | Tutorial Notes

Visual System: Visual Field Deficits

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC8. Fundamental discoveries promote healthy living and treatment of disease.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the distribution of the axons of retinal ganglion cells to major processing centers in the
forebrain and brainstem.
2. Discuss the topographic representation of visual space in the primary visual cortex (V1) and its
anatomical basis in the organization of visual projections.
3. Characterize, using appropriate clinical terms, the visual field deficits associated to damage or
disease along the central visual pathways.

TUTORIAL NARRATIVE

Visual field deficits

A deficit in the visual fields (a region in the visual field of one or both eyes in which there is a loss of
sight) is referred to as a scotoma. You might think that a scotoma would be very obvious to an individual
who has one, and many times they are. But sometimes, especially when it occurs in the periphery, a
scotoma may go unrecognized until the individual has an accident that all too vividly reveals her/his
sensory loss. (Traffic accidents are a common way to uncover such visual field deficits.)
Review the central projections of retinal ganglion cells to targets in the diencephalon and midbrain (see
Figure 12.12 for gross overview and tutorial: “Visual System—Central Visual Pathways”).
On the right side of Figure 12.6, you will see examples of different types of visual field deficits. In each
case, the regions of the visual field of each eye that are affected are shown in black. That is, the part of
the visual field that is not visible in that eye is blacked out. Visual field diagrams are always done for
each eye individually. Some deficits would not be easy to demonstrate if both eyes were open during
the testing. On the left of the figure, lines are drawn through parts of the visual pathways to indicate
locations that could be damaged to give each of the illustrated patterns of deficits.

1
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 Visual Field Deficits

Some rather cumbersome names are used to refer to particular patterns of visual field deficits. Anopsia
(also spelled anopia) simply means loss of sight in one or both eyes. Hemianopsia indicates loss of sight
in one half of the visual field. Quadrantanopsia is a loss of sight in one quadrant of the visual field.
Bitemporal hemianopsia is a loss of sight in the right visual field of the right eye and the left visual field
of the left eye. It is also called heteronymous hemianopsia because the affected regions of the visual
fields in the two eyes are not congruent. When the affected regions of the visual fields of both eyes
overlap (i.e., loss of vision in the left or right visual field of both eyes), the deficit is called homonymous.
A patient could be described as having a homonymous hemianopsia or a homonymous
quadrantanopsia, etc.
Widespread loss of vision without damage to the most central part of the visual field representation is
called macular sparing. Macular sparing is a phenomenon often associated with lesions in the visual
cortex but it can be found with lesions along the length of the visual pathways.
Consider the visual field deficits shown in Figure 12.6 and identify each by the proper clinical term (or
combination of terms) highlighted on this page in bold font. You should be able to relate this figure back
to previous figures on visuotopy and explain why each visual field deficit is associated with damage to
the particular structure along the visual pathway from retina to visual cortex.

STUDY QUESTIONS
Q1. Patient 1. A patient complains of bumping into objects on the right, especially objects such as
chairs and tables that are at waist height or below. You suspect a visual field deficit involving
which structure(s)?
A. lesion in the left eye or left optic nerve
B. lesion in the right eye or right optic nerve
C. lesion in the optic chiasm
D. lesion in the left Meyer’s loop
E. lesion in the right Meyer’s loop
F. lesion in the left parietal white matter
G. lesion in the right parietal white matter
H. lesion in the left cuneus gyrus
I. lesion in the right cuneus gyrus
J. lesion in the left lingual gyrus
K. lesion in the right lingual gyrus

Q1. Patient 2. A patient undergoes neurosurgery to remove an operable tumor (an early stage
glioblastoma, which arises in white matter) from the right temporal lobe. Upon recovery in the
acute care setting, the patient’s caregivers discover that when resting in bed she doesn’t readily
notice visitors approaching from her left. What visual structure may have been injured in this
surgical procedure?
A. lesion in the left eye or left optic nerve
B. lesion in the right eye or right optic nerve
C. lesion in the optic chiasm
D. lesion in the left Meyer’s loop

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 Visual Field Deficits

E. lesion in the right Meyer’s loop

F. lesion in the left parietal white matter
G. lesion in the right parietal white matter
H. lesion in the left cuneus gyrus
I. lesion in the right cuneus gyrus
J. lesion in the left lingual gyrus
K. lesion in the right lingual gyrus

3
 Pupillary Light Reflex

Medical Neuroscience | Tutorial Notes

Visual System: Pupillary Light Reflex

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the distribution of the axons of retinal ganglion cells to major processing centers in the
forebrain and brainstem.
2. Discuss the neuroanatomical basis for the pupillary light reflex.

TUTORIAL OUTLINE

I. Overview of Central Visual Pathways

A. central projections of the retina arise from retinal ganglion cells
B. among the targets of these central projections are a set of nuclei just anterior to the
tectum of the midbrain, in a transitional region between the diencephalon and the
mesencephalon called the pretectum (see Figure 12.12 for gross overview and )
1. pretectum: coordinates the pupillary light reflex (see Figure 12.2)
a. afferent (sensory) limb
i. inputs reach the pretectal nuclei from the ipsilateral optic tract
ii. thus, each side of the pretectum receives input from both eyes
b. efferent (motor limb)
i. the pretectal nuclei send projections bilaterally to the Edinger-
Westphal nuclei
ii. parasympathetic, preganglionic outputs leave the brainstem
through the oculomotor nerve and govern the activity of
constrictor muscles in the iris (pupillary constriction) via
ganglionic input from the ciliary ganglion

1
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 Pupillary Light Reflex

iii. pupillary dilation is under the control of the sympathetic

division of the visceral motor system, with preganglionic
neurons in the upper thoracic spinal cord (intermediolateral cell
column)
2. pretectum is also involved in coordinating the activities of the preganglionic
neurons that innervate the ciliary muscles and allow for accommodation
(changing the shape of the lens)

2
 Pupillary Light Reflex

STUDY QUESTIONS
Q1. Patient 1. During a physical exam, you shine a light into a patient’s left eye and you note that
both pupils react only sluggishly to light. You stimulate the right eye and you find a brisk
constriction of both pupils. From this information alone, what sort of neurological problem
might you suspect?
A. lesion in the left eye or left optic nerve
B. lesion in the right eye or right optic nerve
C. lesion in the left optic tract
D. lesion in the right optic tract
E. lesion in the left Edinger-Westphal nucleus or left oculomotor nerve
F. lesion in the right Edinger-Westphal nucleus or right oculomotor nerve
G. insufficient sympathetic tone to the left iris.
H. insufficient sympathetic tone to the right iris.

Q2. Patient 2. A patient has come to you complaining of double vision. His left eye fails to adduct
when he makes eye movements to the right. His left eyelid droops (ptosis) and the pupil in his
left eye is larger than the pupil in the right. The pupil in the left eye does not react to light nor
does it respond when light is shown in the right eye. How would you explain this deficit in the
pupillary light reflex?
A. lesion in the left eye or left optic nerve
B. lesion in the right eye or right optic nerve
C. lesion in the left optic tract
D. lesion in the right optic tract
E. lesion in the left Edinger-Westphal nucleus or left oculomotor nerve
F. lesion in the right Edinger-Westphal nucleus or right oculomotor nerve
G. insufficient sympathetic tone to the left iris.
H. insufficient sympathetic tone to the right iris.

Q3. Patient 3. A third patient comes to see you with ptosis of his left eye. You examine his eye
movements and these seem normal. Then you notice that the pupil in his left eye is measurably
smaller than that of his right eye. How do you account for the symptoms in this case?
A. lesion in the left eye or left optic nerve
B. lesion in the right eye or right optic nerve
C. lesion in the left optic tract
D. lesion in the right optic tract
E. lesion in the left Edinger-Westphal nucleus or left oculomotor nerve
F. lesion in the right Edinger-Westphal nucleus or right oculomotor nerve
G. insufficient sympathetic tone to the left iris.
H. insufficient sympathetic tone to the right iris.

3
 Auditory System—Peripheral Mechanisms

Medical Neuroscience | Tutorial Notes

Auditory System—Peripheral Mechanisms

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC6. The brain makes it possible to communicate knowledge through language.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the biomechanics of sensory transduction in the middle and inner ear, including the
tonotopy of the basilar membrane.
2. Characterize the neurophysiology of sensory transduction in auditory hair cells.

TUTORIAL OUTLINE

I. Introduction to the Auditory System

A. overview of auditory function: the auditory system transduces sound waves into distinct
patterns of neural activity that are then integrated with other sensations and
motivations to guide behavior
1. sound waves are collected and amplified by physical structures in the external
and middle ear for transfer to neural elements in the inner ear
2. the biomechanical properties of the inner ear decompose complex sound waves
into sinusoidal components, so that component frequencies, their amplitude,
and their phase can be encoded in the firing of the receptor cells
3. in the inner ear and throughout central processing stations, tonotopy is
preserved; i.e., the systematic representation of sound frequency
4. in the brainstem, the auditory information is first processed and divided into
several parallel pathways, some of which compare the signals derived from the
two ears, a process that allows for the localization of sounds in space
5. in addition to local processing of auditory signals, brainstem centers relay
information to the midbrain, which in turn projects to the auditory thalamus

1
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1
 Auditory System—Peripheral Mechanisms

6. the auditory cortex then receives input from the thalamus and processes more
complex aspects of sounds, such as those related to human speech
II. Sound
A. comes from spherical pressure waves generated by vibrating air molecules (see Figure
13.12) that can be characterized by their amplitude (loudness), frequency (pitch) and
phase (temporal displacement) (see Figure 13.2)
B. most natural sounds (human speech, for example) are acoustically complex
C. humans can detect sound in the frequency range of 20 Hz to 20 kHz
III. The ear
A. external ear (pinna, concha, auditory meatus) (see Figure 13.3)
1. gathers sound energy and focuses it on the tympanic membrane (ear drum)
2. filters different sound frequencies to provide cues about sound localization
B. middle ear (tympanic membrane, ossicles)
1. transmit acoustic energy from air to the inner ear
2. amplifies the pressure of acoustic energy some 200-fold
C. inner ear (cochlea, auditory nerve)
1. two-fold function:
a. biomechanical: decompose complex acoustic energy into component
sinusoidal waveforms
b. neural (sensory transduction): transduce this mechanical energy into
neural signals that are then communicated to the brain
2. cochlea (Greek, cochlos = snail)
a. basic anatomy (see Figure 13.4)
(i) small, coiled structure surrounded by bone
(ii) bisected by the cochlear partition into two, large fluid filled
channels (scala vestibuli, scala tympani)
(iii) the cochlear partition contains the organ of corti, which
consists of the basilar and tectorial membranes
(iv) the basilar membrane supports inner and outer hair cells; the
inner hair cells are the sensory receptor cells of the cochlea
(v) the cochlear partition contains a smaller, fluid filled channel
(scala media), which is important for maintaining the proper
ionic environment for neural signaling
(vi) the cochlear partition terminates before the apical end of the
cochlea, allowing for continuity between the scala vestibuli and
scala tympani (at the helicotrema)

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 Auditory System—Peripheral Mechanisms

b. functional overview
(i) pressure transmitted by the ossicles of the middle ear causes
the oval window to bulge inward
(ii) this pressure is conducted throughout the fluid of the scala
vestibuli (called perilymph), around the helicotrema and into
the scala tympani, and is relieved by the outward bulging of the
round window
(iii) passage of pressure throughout the channels of the cochlea sets
up vibrations in the basilar membrane (see Figure 13.5)
(iv) movements of the basilar membrane deform the ends of the
inner hair cells leading to the transduction of mechanical energy
into neural impulses (see Figure 13.6)
c. basilar membrane
(i) frequency tuning (refer back to Figure 13.5)
- the membrane is stiffer, thicker and narrower at the
base of the cochlea and wider, thinner and more
flexible at the apex of the cochlea
- thus, the base is tuned for (responds best to) high
frequencies and apex is tuned for low frequencies
- complex sounds cause vibrations of different parts of
the basilar membrane
- tuning is sharpened by an active process involving the
outer hair cells
(ii) sensory transduction (see Figure 13.7-13.10)
- the stereocilia of hair cells protrude into the scala
media, which contains endolymph – a solution that
contains high concentrations of K+
- vibration of the basilar membrane causes a shearing
motion between the basilar and tectorial membranes
- motion bends the stereocilia that protrude from the
apical ends of the inner hairs cells
- deformation of the stereocilia toward the longest
stereocilia leads to inward flow of current through K+
channels and depolarization of the hair cell membrane
- depolarized hair cells release more neurotransmitter on
afferent endings, resulting in an increase in action
potential firing in the auditory nerve
- deformation of the stereocilia away from the longest
stereocilia leads to closure of K+ channels and
hyperpolarization of the hair cell membrane

3
 Auditory System—Peripheral Mechanisms

- hyperpolarized hair cells release less neurotransmitter

on afferent endings, resulting in an decrease in action
potential firing in the auditory nerve
(iii) hearing loss (see Boxes 13A & 13C)
3. for an excellent review of the anatomy and physiology of these peripheral
components of the auditory system, see the animation on the textbook’s
companion website [click here]
4. for an more aesthetically satisfying experience (featuring Bach’s Toccata &
Fugue in D minor), see also this fantastic animation produced by James Huspeth
(Rockefeller University), one of the world’s leading auditory neurophysiologists
[click here]
5. sensory coding in the auditory nerve (see Figures 13.9 & 13.11)
a. temporal code: hair cell potentials and action potentials in the auditory
nerve can follow an acoustical stimulus up to about 3 kHz
b. “labeled-line” code: preserves information about frequency since the
afferent fibers that innervate different parts of the basilar membrane
inherit their tuning (from the basilar membrane)

4
 Auditory System—Peripheral Mechanisms

STUDY QUESTIONS
Q1. Which of the following is the primary function of the three bones in the middle ear?
A. Selective transmission of high-frequency sounds
B. Selective transmission of low-frequency sounds
C. Amplification of sound pressure waves to increase auditory sensitivity
D. Dampening sound pressure waves to prevent damage to the ear
E. Facilitation of fluid drainage from the Eustachian tube

Q2. Which of the following statements about sensory transduction by hair cells is most accurate?
A. Bending of the cilia toward the shortest cilium produces depolarization.
B. Bending of the cilia toward the longest cilium produces hyperpolarization.
C. Neurotransmitter is released by hair cells when the calcium that rushes into the cilia
reaches the active zone at the base of the hair cells.
D. The firing of action potentials in second-order sensory neurons can be either up- or
down-regulated, depending on the direction in which the bundle of cilia (of the afferent
hair cell) is bent.
E. Hair cells are postsynaptic to second-order sensory neurons.

Q3. What explains the tonotopy that is present in the auditory division of CN VIII?
A. The amount of myelin wrapping any given axon: the more myelin, the higher the pitch
encoded by the axon.
B. The location of the cell body in the spiral ganglion: the closer to the center of spiral, the
lower the pitch encoded by the axon.
C. The location of where the peripheral process receives contact from hair cells along the
basilar membrane.
D. The average rate of action potential generation: the higher the average rate of action
potential generation, the higher the pitch encoded by the axon.
E. The number of AMPA receptors in the postsynaptic process: the more AMPA receptors,
the higher the pitch encoded by the axon.

5
 Auditory System—Central Processing

Medical Neuroscience | Tutorial Notes

Auditory System—Central Processing

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.
NCC6. The brain makes it possible to communicate knowledge through language.
NCC7. The human brain endows us with a natural curiosity to understand how the world works.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Identify the neural mechanisms for localizing sounds in space.
2. Discuss the organization of the auditory cortex.

TUTORIAL OUTLINE

I. Central processing of auditory information

A. subcortical pathways (see Figure 13.122)
1. first order neurons: spiral ganglion cells
a. peripheral process innervates inner hair cells
b. central process enters the pontine-medullary junction and bifurcates to
innervate the cochlear nucleus
2. second order neurons: cells in the cochlear nucleus that project to multiple
targets on both sides of the brainstem
a. (contralateral) nucleus of the lateral lemniscus in the upper pons:
involved in detecting presence and temporal properties of sound from
one ear (a monaural pathway)
a. (bilateral) superior olivary complex in the mid-pons: different divisions
of this complex are involved in localizing the sources of sounds in
auditory space
(i) medial superior olive (MSO) (see Figure 13.13): localizes low
frequency sounds based on interaural timing differences

1
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 Auditory System—Central Processing

(ii) lateral superior olive (LSO) (see Figure 13.14): localizes sound
based on interaural intensity differences
3. inferior colliculus
a. all lower auditory projections converge on the inferior colliculus
b. here, for the first time in the auditory system, a complete map of
auditory space is computed in the inferior colliculus
4. auditory thalamus
a. inferior colliculus projects to the medial geniculate complex
b. cells in the MGC are sensitive to particular combinations of sounds with
distinct spectral and temporal characteristics
B. auditory cortex
a. target of the MGC located on the superior aspect of the temporal lobe
b. contains several subdivisions (see Figure 13.15)
i. “core” area or primary auditory cortex that receives highly tonotopic input
from the MGC; also maps binaural interactions
ii. “belt” of additional, higher-order auditory areas
c. asymmetry in structure and function
i. the posterior portion of the auditory belt contains Wernicke’s area, a
division of the auditory cortex that is specialized (in humans) for
comprehending speech
ii. for most people (>99% of right-handers and >90% left-handers), functional
Wernicke’s area is in the left hemisphere
iii. there is a structural asymmetry associated with this functional asymmetry:
the planum temporale (the superior plane of the temporal lobe)
- the left planum temporale is larger in most humans than the right
- the degree of asymmetry is associated with perfect pitch abilities
(greater asymmetry in people with perfect pitch)
iv. activation of the right hemisphere is typically greater in the left when
listening to music, compared to listening to speech and environmental
sounds (see Box 13E)

2
 Auditory System—Central Processing

STUDY QUESTIONS
Q1. Which of the following most depends upon the utilization of bilateral auditory information?
A. frequency discrimination
B. sound localization
C. distinguishing pitch from timbre
D. encoding of speech sounds
E. detection of very faint sounds

Q2. Which auditory structure first displays pronounced selectivity for specific combinations of sound
frequencies in the auditory pathway?
A. cochlear nucleus
B. lateral superior olive
C. medial superior olive
D. nuclei of the lateral lemniscus
E. inferior colliculus
F. medial geniculate complex
G. auditory cortex

3
 Vestibular System—Peripheral Mechanisms

Medical Neuroscience | Tutorial Notes

Vestibular System—Peripheral Mechanisms

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Describe the anatomy of the vestibular labyrinth.
2. Describe the biomechanics of sensory transduction in the vestibular labyrinth, including the
biophysics of hair cell sensory transduction.

TUTORIAL OUTLINE

I. Overview
A. vestibular labyrinth is an extension of the inner ear designed to sense the motions that
arise from head movements and the inertial effects due to gravity (see Box 14A2)
1. static head position and linear accelerations of the head are sensed by hair cells
in the otolith organs
2. rotational accelerations are sensed by hair cells in the semicircular canals
A. vestibular signals are relayed to integrative centers in the brainstem and cerebellum,
where it is used to adjusted postural reflexes and eye movements
B. vestibular signals also reach parts of the parietal cortex, where our normal sense of
orientation in three-dimensional space is constructed and (should pathology present) a
sense of dizziness with abnormal vestibular stimulation

II. Peripheral vestibular systems

A. anatomy of the vestibular labyrinth (see Figure 14.1)
1. set of interconnected canals that arise from the same embryological precursor
(otic placode) as the cochlea
2. canals are filled with endolymph (high K+ / low Na+) and surrounded by
perilymph (low K+ / high Na+)
1
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 Vestibular System—Peripheral Mechanisms

3. two classes of sensory structures in each side of the head:

a. two otolith organs: the utricle and sacculus
b. three semicircular canals arranged orthogonally to one another
4. within each sensory structure, there are hair cells that transduce motion signals
into neural impulses
5. hair cells are innervated by the vestibular division of cranial nerve VIII (cell
bodies reside in Scarpa’s ganglia)
B. vestibular hair cells
1. sensory transduction (see Figure 13.8, 14.2 A,B)
a. deformation of stereocilia toward the largest stereocilium leads to
depolarization and increased release of neurotransmitter on peripheral
endings of afferent fibers
b. deformation away from the largest stereocilium leads to
hyperpolarization and decreased release of neurotransmitter
2. orientation of hair cells in sensory structures (see Figure 14.2C)
a. common principle: hair cells (stereocilia) are arranged in parallel to the
direction of biomechanical motion within the sensory structure
b. semicircular canals
(i) hair cells in ampullae are arranged in one orientation so that
motion of endolymph in one direction will depolarize hair cells,
and motion in the opposite direction will hyperpolarize
c. otolith organs
(i) hair cells in the maculae of the utricle and sacculus are arranged
into two populations with opposing orientations along an axis of
mirror symmetry
(ii) motion in one direction will depolarize one subpopulation of
hair cells and hyperpolarize the other
C. mechanism of otolith organ function
1. macula: sensory epithelium of the otolith organs
a. consists of a hair cells and supporting cells, and an overlying gelatinous
layer (the otolithic membrane) upon which are embedded crystals of
calcium carbonate, called otoconia
b. the hair cells protrude into this gelatinous layer, which is heavier than
the surrounding epithelium and fluids
2. when the head is tilted, gravity causes the gelatinous membrane to shift relative
to the underlying epithelium; this displaces the hair cell stereocilium and leads
to tonic depolarization and hyperpolarization (see Figure 14.5)

2
 Vestibular System—Peripheral Mechanisms

3. with linear acceleration, the same sort of shearing motion is induced because
the heavier otolithic membrane transiently lags behind the sensory epithelium;
this leads to phasic depolarization and hyperpolarization of the hair cells
4. the utricular maculae are orientated more or less horizontally and, therefore,
sense movements of the head in the horizontal plane
5. the saccular maculae are oriented roughly vertically and sense up and down
movements of the head, as well as head tilts in the sagittal plane
D. mechanism of semicircular canal function
1. ampulla
a. bulbous expansion at the base of the semicircular canals that contains
the sensory epithelium (called the crista) and an overlying gelatinous
mass (called the cupula) into which the stereocilium of the hair cells
protrude (see Figure 14.7)
b. the cupula creates a barrier for the flow of endolymph around the
semicircular canal
2. when the head is rotated in the plane of the semicircular canal, the inertia of
the endolymph produces a transient force that distends the cupulla away from
the direction of rotation (see Figure 14.8A,B)
3. distension of the cupulla deflects the stereocilia of the hairs cells, which leads to
depolarization or hyperpolarization of the hair cells within any given crista
4. semicircular canals are paired on the two sides of the head (see Figure 14.8C):
a. left horizontal and right horizontal
b. left anterior (superior) and right posterior
c. left posterior and right anterior (superior)
5. rotation of the head in one direction will depolarize the hair cells in one
member of the pair and hyperpolarize the hair cells in the other (see Box 14C)
a. thus, pairs of horizontal canals function in a “push-pull” manner
b. the central processing of vestibular afferents reflects the balance of
activity arising from the paired semicircular canals

3
 Vestibular System—Peripheral Mechanisms

STUDY QUESTIONS
Q1. When looking up into the night sky (while standing), which of the following events happened
deep in the vestibular labyrinth?
A. The superior (anterior) semicircular canals on both sides of your head were phasically
activated during the backward tilt of your head.
B. The horizontal semicircular canals on both sides of your head were phasically activated
during the backward tilt of your head.
C. The posterior semicircular canals on both sides of your head were phasically activated
during the backward tilt of your head.
D. All of the hair cells in the utricles on both sides of your head were depolarized while you
maintained your head in a backward tilt.
E. About half of the hair cells in the sacculus on both sides of your head were depolarized
while you maintained your head in a backward tilt.

Q2. When riding a “merry-go-round” (that rotates in the counterclockwise direction), which of the
following events happened deep in the vestibular labyrinth?
A. The superior (anterior) semicircular canals on both sides of your head were phasically
activated during the acceleration of the ride.
B. The posterior semicircular canals on both sides of your head were phasically activated
during the acceleration of the ride.
C. The left horizontal semicircular canal was activated.
D. The right horizontal semicircular canal was activated.
E. All of the hair cells in the utricles on both sides of your head were depolarized while the ride
was at full operating speed.

4
 Vestibular System—Central Processing

Medical Neuroscience | Tutorial Notes

Vestibular System—Central Processing

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Discuss the neuroanatomy and function of the vestibulo-ocular reflex.
2. Characterize the contributions of vestibulo-spinal projections in postural control.
3. Discuss the contributions of vestibular sensation to proprioception.

TUTORIAL OUTLINE

I. Overview
A. vestibular labyrinth is an extension of the inner ear designed to sense the motions that
arise from head movements and the inertial effects due to gravity (see Box 14A2)
1. static position and linear accelerations are sensed by hair cells in the otolith
organs
2. rotational accelerations are sensed by hair cells in the semicircular canals
B. vestibular signals are relayed to integrative centers in the brainstem and cerebellum,
where it is used to adjusted postural reflexes and eye movements
C. vestibular signals also reach parts of the parietal cortex, where our normal sense of
orientation in three-dimensional space is constructed and (should pathology present) a
sense of dizziness with abnormal vestibular stimulation

II. Central vestibular processing

A. central processes of ganglion cells project via the vestibular division of the eighth cranial
nerve to vestibular nuclei in the rostral medulla and caudal pons, and directly to the
“vestibulocerebellum” (flocculonodular lobe of the cerebellum)
B. one major function of the vestibular nuclei is to coordinate movements of the eyes and
head to allow for stable visual fixation during head or whole body movements
1
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 Vestibular System—Central Processing

C. vestibulo-ocular reflex
1. rotational movements of the head induce eye movements opposite to the
direction of rotation, thus allowing maintained visual fixation of both eyes
2. pathway (see Figure 14.10)
a. input from the horizontal canals reaches the vestibular nuclei on the
two sides of the medulla/pons
b. each vestibular nucleus in turn sends a excitatory projections to the
contralateral abducens nucleus
c. the abducens nucleus directly innervates the ipsilateral lateral rectus
muscle, which pulls that eye toward the lateral side (i.e., abduction)
d. other cells in the abducens nucleus cross the midline again and project
to the opposite oculomotor nucleus, which innervates the ipsilateral
medial rectus causing that eye to turn toward the midline (i.e.,
adduction)
e. to facilitate this excitatory action, there are also inhibitory projections
from the vestibular nuclei to the ipsilateral abducens nucleus
f. this inhibitory projection turns off the excitatory output of the cranial
nerve nuclei (opposite abducens and oculomotor nuclei) that drive the
antagonistic muscles
3. vestibular nystagmus
a. nystagmus = rhythmic form of reflexive eye movements composed of
slow component in one direction interrupted repeatedly by fast
saccadic-like movements in the opposite direction
b. vestibular nystagmus is normally driven by persistent rotation of the
head; the slow component is driven by the vestibulo-ocular reflex and
the fast (“saccadic”, see below) component that resets eye position
c. the balance between the activities of VIII n. afferents that arise from the
functional pairs of semicircular canals determines the type and direction
of nystagmus expressed
d. pathological alteration in the balance of activity between the two sides
can cause the expression of nystagmus (and other vestibular-evoked
signs and symptoms) under conditions that normally would not induce
this ocular motor behavior
D. postural reflexes
1. another major function of the vestibular nuclei is to make reflexive adjustments
of posture that compensate for movements of the head
2. descending projections from the vestibular nuclei reach the medial aspect of the
ventral horn of the spinal cord via medial and lateral vestibulospinal pathways
(see Figure 14.11)

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 Vestibular System—Central Processing

a. medial vestibulospinal projection to the upper cervical cord that

regulates head and neck position
b. “lateral” vestibulospinal projection to motor neurons in the medial
ventral horn that excite extensor muscles in the trunk and limbs; this
pathway mediates balance and maintenance of an upright posture
E. vestibular perception
1. vestibular signals also ascend to the cerebral cortex where they reach conscious
perception (see Figure 14.12)
2. vestibular nuclei sends axons bilaterally that synapse in the ventral posterior
complex of the thalamus on both sides of the brain
3. these vestibular-receptive neurons in the thalamus project to the lateral part of
the somatic sensory cortex (specifically, Brodmann’s Area 3a and a part of
Brodmann’s Area 2), near the face representation; these same areas also
represent other somatic sensory modalities, so it is not clear if there is a
dedicated “primary vestibular cortex”
4. other thalamic projections to parietal area 5 also contribute and, together with
higher-order connections in parietal cortex, integrate somatic sensory
proprioception, visual information about movement, and vestibular
proprioception to construct a body schema relative to 3D space
F. other vestibular connections
1. vestibular nuclei also receive input from most other sensory modalities in order
to guide orienting movements of the head toward relevant stimuli
2. vestibular nuclei receive input from the cerebellum (cortex and deep nuclei)
that modulate vestibular output to ocular motor nuclei and spinal cord

3. vestibular output is also directed toward certain autonomic centers in the

reticular formation of the medulla, which mediate nausea sensations and
influence states of consciousness

STUDY QUESTION
Stare straight ahead at some frontal fixation target. Now turn your head to the right without breaking
fixation. What just happened?
A. The left horizontal semicircular canal was phasically activated during the rightward turn of
your head.
B. The motor neurons in your right oculomotor nucleus that innervate the right medial rectus
muscle just increased their firing rate.
C. The motor neurons in your right abducens nucleus that innervate the right lateral rectus
muscle just increased their firing rate.
D. An inhibitory neuron projecting from the left abducens nucleus to the right oculomotor
nucleus just suppressed the activation of the right lateral rectus muscle
E. Your eyes rotated in the orbits to the right along with your head turn.

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 Chemical Senses—Overview & Olfaction

Medical Neuroscience | Tutorial Notes

Chemical Senses—Overview & Olfaction

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Characterize the peripheral and central organization of the olfactory system.
2. Discuss sensory transduction in olfactory receptor cells.
3. Describe information coding in the olfactory system.

TUTORIAL OUTLINE

I. Overview of the chemical senses

A. special sensory systems in the face—in the nose, mouth and eyes—are capable of
detecting minute quantities of chemical molecules in the environment
1. airborne molecules give rise to:
a. olfactory (smell) sensations via the olfactory system; and
b. noxious (nociceptive) sensations in the oral and nasal cavities, and in
the corneas and conjunctiva of the eyes via the trigeminal
chemosensory system
2. ingested (mostly water-soluble) molecules give rise to gustatory (taste)
sensations via the gustatory system
B. the chemical senses provide a wealth of information across multiple domains of human
behavior; they provide important cues that are relevant to:
1. nutrition (palatable and desirable foods and drink; unpalatable or potentially
harmful foods and drink)
2. physiological functions (visceral motor activities, reproductive cycles, infant-
paternal behavior)
3. social interactions (self and others)

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 Chemical Senses—Overview & Olfaction

4. safety (harmful volatile chemicals in the environment)

5. even hedonic rewards (attractive perfumes, flower scents, pleasurable food
tastes, human pheromones?)
C. thus, the chemical senses can be powerful sources of motivation that can profoundly
influence human (and animal) behavior

II. Organization of the olfactory system

A. anatomical overview (see Figure 15.12)
1. airborne molecules, called odorants, enter the nasal cavity (passively or during
active sniffing) where they diffuse through a layer of mucus and interact with
olfactory receptor neurons in the olfactory epithelium
2. the axons that arise from the receptors cells project through the cribriform plate
and synapse in the olfactory bulb, which is a telencephalic structure connected
to the olfactory cortex by the lateral olfactory tract (despite its appearance, this
is not a nerve!)
3. the projections neurons of the olfactory bulb, called mitral cells, send their
axons to the olfactory cortex, which is comprised of a large set of cortical areas
in the ventral-medial surface of the forebrain, including:
a. piriform cortex (in junction of temporal lobe and posterior frontal lobe)
b. olfactory tubercle (actually, part of the ventral striatum)
c. cortical divisions of the amygdala
d. entorhinal cortex (part of the hippocampal formation in
parahippocampal gyrus)
4. different parts of the olfactory cortex are extensively interconnected and many
parts project to other cortical and subcortical regions, including the thalamus,
hypothalamus and the orbital-medial prefrontal cortex
5. two exceptional aspects of organization worth noting:
a. the olfactory system is the one sensory system that does not relay
information through the thalamus before reaching the cortex
b. the olfactory cortex has no (known) map of the sensory environment or
the sensory epithelium
B. sensory transduction
1. at the apical end of olfactory receptor neurons, there are olfactory cilia that
extend into a thick layer of mucus (see Figure 15.7A)
2. odorants bind to specific molecular receptors located in the plasma membrane
of the cilia
3. a sequence of molecular reactions lead to the depolarization of the olfactory
receptor neuron and the generation of a receptor potential (see Figure 15.11)
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Figure references to Purves et al., Neuroscience, 5 Ed., Sinauer Assoc., Inc., 2012. [click here]

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 Chemical Senses—Overview & Olfaction

a. odorant binding activates an olfactory-specific G-protein (Golf, a member

of the 7-transmembrane, G-protein linked receptor family)
b. activated G-proteins, in turn, activate an olfactory-specific adenylate
cyclase, which increases the production of cAMP
c. cAMP opens cation-selective ion channels that allow influx of Na+ and
Ca++; this leads to the depolarization of the receptor neuron
d. activation of a Ca++-gated, Cl- conductance allows for the efflux of Cl- and
further adds to the depolarization
e. if threshold is reached, then action potentials are generated at the base
of the receptor neuron and transmitted to the olfactory bulb via the
olfactory nerve (cranial nerve I)
4. olfactory receptor neurons adapt in the continued presence of an odorant (a
familiar experience to all)
a. Ca++ binds to calmodulin (CAM) and the Ca++-CAM complex interacts
with the cation-selective channel and reduces its sensitivity to cAMP
b. removal of Ca++ via the Na+/Ca++ exchanger reduces the intracellular
concentration of Ca++ ; this reduces the receptor potential
C. olfactory coding & perception
1. odorant-receptor interactions
a. humans are sensitive to odorants in the nanomolar to millimolar
concentration ranges
i. small changes in molecular structure can lead to major changes
in perception (e.g., D-carvone smells like rye, but L-carvone
smells like spearmint)
ii. the quality of an odor evoked by an odorant depends on its
concentration (e.g., low concentrations of indole smell like a
floral bouquet, but high concentrations smell putrid)
iii. most natural odors are a complex mixture of a least several
odorants at different concentrations
b. some individuals lack certain genes that encode particular olfactory
receptors and are anosmic for certain odorants
2. the “logic” of olfactory coding
a. different odors activate molecularly and spatially distinct subsets of
olfactory receptor neurons (ORNs) in the olfactory epithelium
i. different olfactory receptor genes are expressed in subsets of
ORNs that are distributed in bilaterally symmetrical zones of the
olfactory epithelium
ii. however, most ORNs expresses only one allele of about 400
olfactory receptor genes

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 Chemical Senses—Overview & Olfaction

- some olfactory receptor proteins are activated by

just one type of odorant molecule
- but others are activated by a number of different
odorant molecules
- thus, there is a “combinatorial code” (rather than a
labeled-line code) of olfactory receptors, with
receptor encoding the molecular shape of odorants
b. convergence of ORN axons in the olfactory bulb
i. the principle cells of the olfactory bulb, called mitral cells, send
dendrites into complexes of synapses (neuropil) called
glomeruli (see Figure 15.14D)
ii. each glomerulus receives input from about 25,000 ORNs, with
each of these ORNs expressing the same olfactory receptor
protein!
- this remarkable convergence may maximize the
fidelity and sensitivity of odorant detection
iii. all the ORNs that express the same olfactory receptor allele
converge onto a small subset of bilaterally symmetrical
glomeruli in the two olfactory bulbs
iv. each glomerulus also contains synaptic connections of
additional cell types in the olfactory bulb, including tufted cells,
periglomerular cells and granule cells
- granule cells are thought to mediate lateral
inhibitory connections across mitral cells
- granule cells may participate in plasticity of neural
circuits in the olfactory bulb
c. to solve the problem of coding complex odors, the olfactory bulb
employs a sparse coding mechanism, with a relatively small number of
glomeruli activated by a subset of dominant molecular shapes that may
be present in complex odors
d. temporal coding in the olfactory cortex
i. the convergence of molecular information in the olfactory bulb
is apparently lost in the projections of mitral cells to the
olfactory cortex
- a single odorant produces activation in neurons that
are broadly distributed across the olfactory cortex
- mitral cells that receive input from the same
glomerulus make synaptic connections with
neurons throughout a large extent of the olfactory
cortex

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 Chemical Senses—Overview & Olfaction

ii. thus, in the absence of an obvious spatial code and a map of the
olfactory epithelium in the olfactory cortex, olfactory
perception is likely based upon a temporal code
iii. central olfactory structures oscillate (i.e., firing nearly
synchronous patterns of action potentials) when particular
odorants are presented
3. physiological effects of odorants
a. olfactory information reaches a variety of integrative centers in the
forebrain that allow olfactory cues to influence cognitive, visceral,
emotional and homeostatic behaviors
i. the piriform cortex sends input to the orbital-medial prefrontal
cortex (see Figure 15.1C), where multimodal input related to
complex stimuli—such as food—becomes integrated
ii. the piriform cortex also projects to the mediodorsal thalamic
nucleus, which projects to the prefrontal cortex, including the
dorsal-lateral sector where olfactory signals may be used to
guide working memory (e.g., search or tracking behavior)
iii. olfactory projections to the entorhinal cortex (parahippocampal
gyrus) are implicated in olfactory based memory acquisition and
memory recall
b. in many species (possible including humans), species-specific odorants
called pheromones play an important role in influencing social
interactions and reproductive behavior (although humans lack a
vomeronasal organ, which tranduces pheromone signals in most
mammals)
c. the ability to detect and discriminate odors normally decreases with age
(see Figure 15.5B)
d. the ability to detect and discriminate odors may be lost following
traumatic head injury, if the axons of CN I are severed by movement of
the brain relative to the cribiform plate (see Figure 15.1A-B)
i. however, some olfactory function may recover with the
regrowth of ORN axons to the olfactory bulb
ii. ORNs normally undergo a cycle of degeneration and
replacement by new ORNS that differentiate from a population
of neuronal stem cells from among the basal cells in the
olfactory epithelium (see Figure 15.7A)
iii. regeneration of ORNs, regrowth of ORN axons to the olfactory
bulb, specific targeting of ORN axons to the correct glomeruli,
and plasticity in central olfactory circuits may not be 100%
efficient, so olfactory perception may remain permanently
altered following recovery from head trauma

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 Chemical Senses—Overview & Olfaction

STUDY QUESTION
Which of the following statements concerning the encoding of olfactory signals is most accurate?
A. Most olfactory receptor neurons express a large number of different olfactory receptor genes.
B. There is a “labeled-line code” connecting the olfactory epithelium to the olfactory bulb, with a
1-to-1 mapping of olfactory receptor neurons to glomeruli.
C. There is a “combinatorial code” operating in the olfactory cortex, since individual cortical
neurons respond selectively to just one odorant.
D. Central olfactory structures operate using a “temporal code”, since nearly synchronous
oscillations in neural activity are broadly distributed when particular odorants are presented.

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 Chemical Senses—Gustation

Medical Neuroscience | Tutorial Notes

Chemical Senses—Gustation

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Characterize the peripheral and central organization of the gustatory system.
2. Discuss sensory transduction in gustatory receptor cells.
3. Describe information coding in the gustatory system.

TUTORIAL OUTLINE

I. Organization of the gustatory system

A. anatomical overview (see Figure 15.172)
1. chemical constituents of foods interact with taste receptors cells located on
epithelial specializations, called papillae, which contain the taste buds (see
Figure 15.18)
2. taste buds are distributed on the tongue, soft palate, epiglottis, pharynx and
upper esophagus
3. taste receptor cells make synapses on the peripheral axons of cranial nerves VII,
IX and X
a. anterior tongue (soft palate)  facial nerve (CN VII)
b. posterior tongue  glossopharyngeal nerve (CN IX)
c. epiglottis (esophogus)  vagus nerve (CN X)
4. these central axons project into the solitary tract and synapse in the rostral
division of the nucleus of the solitary tract
a. the posterior division of this nucleus is a visceral sensory relay (more on
that in Unit 4 of this course)

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 Chemical Senses—Gustation

b. integration of gustatory and visceral sensory inputs across the rostral-

caudal axis of this nucleus facilitates appropriate visceral motor
activities in response to harmful tastants, such as gagging or vomiting
5. the nucleus of the solitary tract projects to a distinct part of the ventral
posterior complex in the thalamus
6. this part of the ventral posterior complex projects to several cortical areas,
including areas in the rostral insula and the frontal operculum (in the depth of
the rostral lateral fissure)
7. these cortical regions are interconnected with the posterior orbital prefrontal
cortex, where olfactory, gustatory and somatic sensory information is combined
to produce flavor sensations from which the hedonic values of foods are
represented
B. sensory transduction (see Figure 15.20)
1. taste receptor cells have a variety of transduction mechanisms (see Figure 15.21)
a. some tastants interact with receptors on ion channels in the apical tip of
the cell; the opening of Na+ channels or the closing K+ channels leads to
the generation of a receptor potential
b. other tastants interact with G-protein coupled receptors that use
second messengers to elevate intracellular Ca++ concentrations and
depolarize the membrane
2. depolarization and elevated intracellular Ca++ leads to the exocytosis of a
chemical neurotransmitter (serotonin), which binds to receptors on the sensory
axon
C. gustatory coding & perception
1. tastant identity is encoded by the activation of different receptors that are most
sensitive to distinct chemical substances (see Figure 15.19)
a. there are receptors that are especially sensitive to:
i. sucrose (sweet)
ii. NaCl (salt)
i. HCl (acid)
ii. quinine (bitter)
iii. glutamate (Japanese, “umami” = “delicious”)
b. detection thresholds are higher for substances that are important in our
diet (e.g., salts and carbohydrates); in the millimolar range
c. detection thresholds are lower for potential harmful compounds (bitter-
tasting alkaloids); in the nanomolar range
2. the concentration of a tastant is generally correlated with the number of
receptor cells activated and the intensity of afferent activation, as well as the
perceived intensity of the taste

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 Chemical Senses—Gustation

3. in central gustatory centers, as in olfactory centers, there are no obvious ‘maps’

or systematic representations of tastants or the sensory periphery
4. the nature of the gustatory code remains obscure, but it appears to operate
according to a “labeled-line” code
i. different tastants activate distinct classes of receptor neurons that
make synaptic contact onto peripheral processes of afferent neurons
that are “labeled” by receptor specificity
ii. the responses of subcortical central neurons are tuned for tastant
identity, reflecting receptor specificity
iii. nonetheless, at higher centers of processing (especially in the orbital
cortex), the hedonic value of food becomes the most salient feature of
representation, rather than the molecular identity of any particular
tastant

STUDY QUESTION
Which of the following statements concerning the encoding of gustatory signals is most accurate?
A. Most gustatory receptor neurons express the full complement of genes that encode the five
basic classes of gustatory receptors.
B. Subcortical gustatory processing appears to implement a “labeled-line code” with the neural
responses of sensory cells reflecting the molecular properties of the gustatory receptors that
drive the response.
C. There is a “combinatorial code” operating in the orbital cortex, since individual cortical neurons
respond selectively to just one tastant.
D. At higher stages of gustatory processing in the brain, the most salient property of food is the
relative concentration of sour, bitter, salty, sweet, and “glutamate-like” tastants.

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 Chemical Senses— Trigeminal Chemosensation

Medical Neuroscience | Tutorial Notes

Chemical Senses—Trigeminal Chemosensation

MAP TO NEUROSCIENCE CORE CONCEPTS1

NCC1. The brain is the body's most complex organ.
NCC3. Genetically determined circuits are the foundation of the nervous system.

LEARNING OBJECTIVES
After study of the assigned learning materials, the student will:
1. Characterize the general organization of the trigeminal chemosensory system.
2. Discuss sensory transduction in polymodal C nociceptive neurons.

TUTORIAL OUTLINE

I. Trigeminal chemoreception
A. polymodal nociceptive (C) fibers in the ophthalmic (e.g., corneas), maxillary and
mandibular (e.g., mucous membranes in nose and mouth) branches of the trigeminal
nerve that are activated by chemical irritants (e.g., air pollutants, ammonia, capsaicin)
(see Figure Box 10A2)
1. irritants activate transient receptor potential (TRP) channels, most of which are
cation-selective ion channels
2. irritants can also activate olfactory and gustatory receptors at low concentration
(non-irritating concentrations)
3. at higher concentrations, they activate the polymodal nociceptive fibers of the
trigeminal system, presumably via the activation of TRP channels (which are
distinct from the channels that operate in olfaction and gustation)
B. the central processes of these fibers synapse in the spinal trigeminal nucleus and project
along with this division of the trigeminal pain & temperature system (see Figure 10.6B)
C. activation of these fibers can lead to a variety of protective physiological responses,
including increased salivation, sweating, tearing, increased nasal secretions,
vasodilation, bronchoconstriction
1. these reactions are protective as they dilute irritant chemicals and help prevent
inhalation or ingestion

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 Chemical Senses— Trigeminal Chemosensation

STUDY QUESTION
If you choose to eat hot and spicy food (as I sometimes do), why does your mouth burn and your scalp
sweat (among other visceral sensory and motor reactions)?
A. Capsaicin and related compounds in spicy food activate transient receptor potential (TRP)
channels on taste cells in taste buds.
B. Capsaicin and related compounds in spicy food activate transient receptor potential (TRP)
channels on free nerve endings of polymodal C nociceptive fibers in oral mucosa.
C. Signals pertaining to the activation of TRP channels are integrated in the nucleus of the solitary
tract in the dorsal tegmentum of the caudal pons and upper medulla.
D. Signals pertaining to the activation of TRP channels are integrated in the spinal trigeminal
nucleus in the lateral tegmentum of the caudal pons and medulla.
E. Central processing of signals derived from TRP channel activation are distributed to integrative
centers in the hypothalamus and brainstem where visceral motor commands are distributed to
sweat-promoting preganglionic (sympathetic) neurons.
F. Central processing of signals derived from TRP channel activation are distributed to higher brain
centers where sensations are elaborated in cortical networks.
G. All of the above.