Learning and Memory

 Learning is the process of acquiring new information.

 Memory is our ability to store and receive information in the brain.
o Procedural memory: learned skills or actions (Ex. Riding a bike).
o Semantic memory: not drawn from personal experience (ex. Names of colors).
o Episodic memory: autobiographical events and experiences.
 Conscious recollection of previous experiences and context (Time, place,
emotions, etc.).
 Hippocampal dependent.

 The hippocampus was named for its resemblance to a sea horse.

 Patient H.M. (Henry Molaison) suffered from severe epilepsy. His hippocampus and
entorhinal cortex were damaged. The medial temporal lobes on both sides were
removed. The surgery had removed the amygdala, hippocampus, and some cortex,
which resulted in severe anterograde amnesia. The cerebellum was dramatically
shrunken.
o He could remember things for a very short time.

 Retrograde amnesia: loss of memories formed before trauma such as surgery.

 Anterograde amnesia: inability to form new memories after onset of a disorder.

 Components of the medial temporal lobe: Optic tract, tail of the caudate nucleus,
hippocampus, lateral ventricle, parahippocampal cortex, entorhinal cortex, and
perirhinal cortex.

 Short-term memory: the capacity to store a small amount of information in the mind
and keep it readily available for a short period of time (Pre-frontal cortex).
 Long-term memory has two subdivisions:
o Declarative: things you know that you can tell others (Can be tested in humans
because we can talk).
o Nondeclarative (Procedural): things you know that you can show (Can be tested
in all animal species).
 Memory consolidation: converting short-term into long-term memory.
o Encoding: Sensory information is passed into short-term memory (First senses).
o Consolidation: Short-term memory information is transferred into long-term
storage (Encoded information linked to existing memories).
o Retrieval: Stored information is used (Repeat other stages repeatedly).
o A problem at any stage can result in memory failure.
 Declarative memory deals with facts and information acquired through learning that can
be stated or described.
o Sensory processing in the cortex  Parahippocampal, Entorhinal, and Perirhinal
cortex  Hippocampus  Medial diencephalon (Mammillary bodies) 
Declarative memory storage in the cortex.
o Damage to either the medial temporal lobe or the medial
diencephalon/mammillary bodies will prevent the formation of any new
declarative memories without the loss of previously formed ones.
 Nondeclarative memory is shown through performance (Non-verbal).
o Skill learning: learning to perform a task requiring motor coordination.
o Priming: exposure to a stimulus facilitates subsequent responses to the same or
similar stimuli.
o Associative learning: the association of two stimuli or of a stimulus and response.

 Operant conditioning: a form of associative learning (Instrumental).

o Animals in a Skinner box can learn to press a lever to gain food pellets.
 Classical conditioning: an initially neutral stimulus predicts an event (Pavlovian).
o Conditioning a dog to salivate at the sound of a bell ringing.
o Step 1: Unconditioned stimulus (US)  Unconditioned response (UR)
o Step 2: Neutral stimulus  No response
o Step 3: Conditioning
o Step 4: Conditioned stimulus (CS)  Conditioned response (CR)

 Long-term memory summary:

o Declarative: things you know that you can tell others.
 Episodic: remembering your first day in school.
 Semantic: knowing the capital of France.
o Nondeclarative: things you know that you can show others.
 Skill learning: knowing how to ride a bike.
 Priming: being more likely to use a word you heard recently.
 Conditioning: salivating when you see your favorite food.
 The hippocampus is crucial for spatial learning (Cognitive maps).
o Place cells in the hippocampus become active when an animal is in or moving
toward a particular location (Hippocampus).
o Grid cells fire when an animal crosses intersection points of an abstract grid
(Entorhinal cortex).
o The firing of entorhinal border cells signals arrival at the perimeter (Entorhinal
Cortex).

 Place cells are spatially modulated neurons found in the hippocampus that underlie
spatial memory and navigation.
o An individual place cell only fires when in a specified location in the current
context. A new context will result in place cell remapping.
 Border and Grid Cells are stable and do not remap.
o Critical for spatial learning and memory.
 After learning, place cell sequences are repeated and fire in sequential order.
o A replay occurs during sleep and is sped up over and over.
o Replay events are also seen during wakefulness and will “replay” in anticipation
of a previously learned task/context.
o Interfering with hippocampal replay disrupts memory.

 Engram (Memory trace): The physical basis of memory in the brain.

 Permanent storage (Consolidation) of information tends to occur in the regions where it
was first processed.
 Retrieval from LTM makes the memory trace plastic again and subject to alteration and
strengthening before reconsolidation.
 Neuroplasticity: Ability of neurons and neural circuits to be remolded by events.
o Synaptic plasticity can be structural or physiological.
  Physiological changes include increased neurotransmitter release and a
greater effect due to changes in neurotransmitter-receptor interactions.
o Inputs from other neurons can also modulate synaptic activity.

 After training, each action potential in the relevant neural circuit causes an increased
release of neurotransmitter molecules. The postsynaptic potential (PSP), therefore,
increases in size.
o An interneuron modulates the polarization of transmitter molecules per impulse.
o A neural circuit that is used more often increases the number of synaptic
contacts. For example, strong activity can induce a synapse to enlarge and
eventually split, creating a perforated synapse.
o A more frequently used neural pathway takes over synaptic sites formerly
occupied by a less active competitor.
 New synapses could form or some could be eliminated with training.
 Training might also lead to the reorganization of synaptic connections.
 Glia also plays a role in learning and synaptic activity. Nearby astrocytes mark which
synapses will change in strength.

 Lab animals living in a complex environment show biochemical and anatomical changes
in the brain. A variety of plastic changes in the brain are linked to the environment.
o Standard condition (SC), impoverished (IC), and enriched (EC).
 Animals in an enriched condition compared to those in the impoverished
have a heavier cortex, enhanced cholinergic activity, and cortical neurons
with more dendritic branches.
o An enlarged image of a neuron quantifies branching.
o There are significant differences in branching, especially in the basal dendrites.

 The sea slug Aplysia is used to study plastic synaptic changes in neural circuits.
 o They have fewer nerve cells, create detailed circuit maps for particular behaviors,
and have little variation between individuals.
o They are capable of nonassociative learning 9A single stimulus is presented once
or repeated).
o Stimulus to the siphon causes gill retraction. Repeating this will cause it to retract
less. This results from fewer transmitters being released (Short-term).
 Habituation: decreased response to repeated presentations of a stimulus.
o Habituation occurs faster and faster. This is due to the retraction of some
synaptic terminals (Long-term).
 Dishabituation: restoration of response amplitude after habituation.
 Sensitization: prior strong stimulation increases response to most stimuli.

 Donald Hebb proposed that when a presynaptic neuron repeatedly activates a

postsynaptic neuron, its connection will become stronger and more stable.
o “Neurons that fire together, wire together.”
 Cell assemblies, linked via Hebbian synapses, could store memories.

 Long-term potentiation: stable and enduring increase in the effectiveness of synapses.

o Response of a postsynaptic neuron after a tetanus (Brief high-frequency burst of
electrical stimulus of the presynaptic neuron): EPSPs were much stronger.
o If axons in the circuit are stimulated only once every second, the response size is
stable. However, after brief tetanus, the size of the EPSP response increases and
remains high.
 The hippocampal formation includes the dentate gyrus (DG) and adjacent cortex.
o The hippocampus has three divisions: CA1, CA2, and CA3.
o The trisynaptic loop displays LTP: DG>CA3>CA1.
 o In CA1, LTP occurs at glutamate synapses (LTP requires NMDA receptors).
Glutamate first activates AMPA receptors. NMDA receptors do not respond until
enough AMPDA receptors are stimulated and the neuron is partially depolarized.
 Normally, the NMDA channel is blocked by an Mg2+ ion, and only the AMPA channel
functions in the neuron's excitation. With repeated activation of AMPA receptors,
depolarization of the neuron drives Mg2+ out of the NMDA channel, and Ca2+ ions enter.
The increase in calcium triggers processes that lead to LTP. Activation of calcium-
dependent protein kinase II increases the conductance of AMPA receptors already
present in the membrane. The synapse is enhanced after the induction of LTP.
Subsequent changes may expand the size of the synapse.
o When AMPA is bound by glutamate, we get a depolarization from EPSPs.
Magnesium ions block NMDA, so it does not get activated. The activation of
AMPA receptors makes an influx of sodium ions that will remove the magnesium
block. Then glutamate can bind to NMDA receptors. Calcium can then enter
through the NMDA receptor.

 Ca2+ influx activates protein kinases (Enzymes that add phosphate groups to protein
molecules). CaMKII (Calcium-calmodulin kinase II), affects AMPA receptors:
o This causes more AMPA receptors to be produced. Moves existing nearby AMPA
receptors into the active synapse.
o Increases conductance of Na+ and K+ ions in membrane-bound AMPA receptors.
o This will increase the synaptic sensitivity to glutamate.
o Retrograde gases can cause more glutamate to be released.

 Strong stimulation of a postsynaptic cell causes it to release a retrograde messenger that

travels across the synapse and alters function in the presynaptic neuron.
o Ensures that more glutamate will be released into the synapse, strengthening it.
o The retrograde signal is triggered by the activation of transcription factor CREB
(cAMP-responsive element-binding protein).
  Activation of NMDA receptors activates CREB and changes gene
expression. The genes can encode new receptors, kinases, or cellular
structural elements.

 LTP may be one part of memory formation.

o Correlational observations: time course of LTP is similar to memory formation.
o Somatic intervention: drug treatments that block LTP impair learning.
o Behavioral intervention: training an animal in a memory task can induce LTP.

 Neurogenesis is the process by which new neurons are formed in the brain. It is crucial
when an embryo is developing. It continues in certain brain regions after birth
throughout our lifespan.
o Subventricular zone and dentate gyrus (Granule cells).
o BrdU (Bromodeoxyuridine) is a label that is incorporated into the DNA of cells
that are about to divide. NeuN (A neuron-specific nuclear protein) labels neurons
to distinguish them from other cells.
 Adult neurogenesis occurs primarily in the dentate gyrus. New neurons and more plastic.
 Conditional knockout studies: turning off neurogenesis reduces spatial learning.