Chapter 17: Learning and Memory

Define learning and memory.

Learning is the process by which experience changes the nervous system and behavior, meaning acquiring new information or skills.
Memory is the ability to store and retrieve that information, plus the specific information that is stored.

Anterograde amnesia

the ability to form new long term memories AFTER the event or injury.

Retrograde amnesia

the loss of memories formed BEFORE the event or injury, often with a gradient where recent memories are more affected

H.M. had which structures removed, and what was the main memory deficit?

H.M. had the anterior temporal lobes removed bilaterally, including both hippocampi, both amygdalae, and surrounding cortex.
He developed severe anterograde amnesia for declarative (episodic and semantic) memories, with relatively intact working memory and nondeclarative learning.

What stayed intact in H.M., and what does that teach us?

Intact: working memory, skill learning (for example mirror tracing, mirror-reversed reading), basic intelligence, and perception.
This shows declarative memory depends on medial temporal lobe structures such as the hippocampus, while nondeclarative memory and working memory rely on other systems like basal ganglia, cerebellum, and cortex.

Medial Temporal Lobe Amnesia

a pattern of memory impairment after damage to medial temporal structures such as the hippocampus and nearby cortex, where declarative memory is strongly impaired, especially forming new episodes and facts, but general intelligence and nondeclarative (skills and habits) memory are relatively preserved.

In the delayed non-matching-to-sample (DNMS) task in monkeys, what must the monkey learn to do?

The monkey sees a sample object covering a food well. After a delay, it sees that old object together with a new object and must choose the new, non-matching object to receive the reward.
This tests recognition or explicit memory for what was seen before, a form of declarative memory.

What happens to DNMS performance after large medial temporal lobe lesions?

Monkeys with large medial temporal lobe lesions perform very poorly, especially at longer delays.
This indicates that the hippocampus and surrounding medial temporal cortex are critical for this kind of declarative recognition memory.

Does removing only the amygdala strongly impair DNMS performance? What does that mean?

Removing the amygdala alone has little effect on DNMS performance.
This suggests the amygdala is not essential for basic declarative recognition in this task, whereas the hippocampus and surrounding cortical areas are crucial.

Perirhinal Cortex

supports familiarity or the feeling that something was seen before.

Parahippocampal cortex

encodes contextual and spatial information about where things occurred.

Hippocampus

supports recollection of complete episodes including who, what, where, and when. specifically also spatial working memory (remembering where something was in space)

Korsakoff’s syndrome

Korsakoff’s syndrome is a severe memory disorder often caused by chronic thiamine (vitamin B1) deficiency associated with long term alcoholism.
It typically damages mammillary bodies, mediodorsal thalamus, and parts of basal frontal cortex.
The result is anterograde amnesia for declarative memories with frequent confabulation.

Sensory buffers

extremely brief storage systems for raw sensory information, lasting milliseconds to a few seconds.

Working memory

short term storage with active manipulation of information, lasting seconds to about 30 seconds and capacity-limited.

Long term memory

Long term memory is very long-lasting storage from days to years with huge capacity.

What are the three components of working memory in the Baddeley model, and what does each do?

The phonological loop holds verbal information such as repeating a phone number.
The visuospatial sketchpad holds visual and spatial information such as a mental map.
The episodic buffer integrates information from different modalities into a unified episode with time and order.

Declarative memory (explicit)

Explicit or declarative memory can be consciously accessed and verbalized and includes facts and events. (stuff you can DECLARE/say)

Nondeclarative memory (implicit)

Implicit or nondeclarative memory is expressed through performance rather than conscious recall and includes skills, priming, and conditioning. (stuff you can only show you know by DOING, not saying).

Episodic memory

Memory of an event. Ex. “I went to Puerto Rico with my family last winter break.”

Semantic memory

Specific fact Ex. “San Juan is the capital of Puerto Rico.”

3 types of nondeclarative memory

Skill learning: improving at playing the piano or riding a bike or mirror tracing.
Priming: being faster to recognize the word “nurse” after seeing the word “doctor.”
Conditioning: salivating when you hear a bell that has been repeatedly paired with food, or freezing to a tone paired with shock.

Which brain region is most important for response learning such as learning to always turn left?

The striatum, which is part of the basal ganglia, is most important for response or habit learning such as consistently turning the same direction for a reward.

Which brain region is most important for object recognition in working memory tasks?

Nonprimary visual cortex, especially extrastriate temporal areas, is critical for object recognition tasks such as knowing which object is novel.

Classical/Pavlovian Conditioning

learning that a neutral stimulus predicts an important event, so the organism learns a stimulus to stimulus association.

Operant conditioning

learning that a behavior is followed by a reward or punishment, so the organism learns a behavior to outcome association.

Define non-associative learning and name its three main forms.

Non-associative learning is a change in the response to a single stimulus due to repeated exposure without pairing with another stimulus or outcome.
Its three main forms are habituation, dishabituation, and sensitization.

In Aplysia’s gill-withdrawal reflex, what happens during habituation at the synaptic level?

Repeated light touch to the siphon produces progressively smaller gill withdrawal.
At the synaptic level, the siphon sensory neuron releases less neurotransmitter onto the motor neuron so the motor neuron is less activated, and with long-term habituation some presynaptic terminals retract.

In Aplysia, what is sensitization and how does it change the gill-withdrawal response?

Sensitization is when exposure to a strong stimulus such as a tail shock increases the response to a later weak stimulus such as siphon touch.
Modulatory interneurons enhance neurotransmitter release from the siphon sensory neuron onto the gill motor neuron, making the gill withdrawal larger and more prolonged.

What is a cognitive map?

A cognitive map is an internal mental representation of spatial relationships between objects and locations in the environment that allows flexible navigation.

Place Cells

neurons in the hippocampus that fire maximally when the animal is in or moving toward a specific location in an environment.

Grid cells

neurons in entorhinal cortex that fire at multiple locations forming a repeating hexagonal grid pattern across space.

Border cells

neurons in entorhinal cortex that fire when the animal is near environmental boundaries such as walls and edges.

Name one type of animal that has an enlarged hippocampus and explain why.

Food-caching birds such as Clark’s nutcrackers or food-hiding mammals have enlarged hippocampi because they must remember many cache locations and rely heavily on spatial memory.
Similarly, London taxi drivers show larger posterior hippocampi due to intense demands for spatial navigation.

What are the three main stages of memory processing for long-term declarative memory?

Encoding is processing and transforming sensory input into a format that can be stored.
Consolidation is stabilizing the encoded information into long term memory and is hippocampus dependent early on.
Retrieval is accessing stored information to guide behavior or conscious recall.

What is reconsolidation, and why is it important?

Reconsolidation is the process by which a retrieved memory becomes temporarily unstable and then is re-stored.
During reconsolidation, memories can be strengthened, modified, or distorted, which explains how recall can update or change memories.

Are long-term memories permanently stored in the hippocampus? Where are they thought to be stored?

Long term memories are not permanently stored in the hippocampus.
They are thought to be stored in distributed networks across cortex, especially in the same regions that originally processed the information, while the hippocampus is crucial for initial consolidation and indexing.

Laminar organization

Laminar organization means cortex has six layers, each with characteristic cell types and connectivity.

Columnar organization

Columnar organization means neurons form vertical columns through these layers that share similar response properties and are heavily interconnected.

The Engram

The engram is the physical and biochemical trace of a memory in the brain, essentially the pattern of synaptic changes and neural circuitry that encodes a particular memory.

Why is cortical layer I considered a candidate site for storing memory traces?

Cortical layer I contains many dendrites and synapses but few cell bodies, making it rich in potential sites for synaptic modification.
Its horizontal connections and integration across columns make it a plausible substrate for distributed engram storage.

How do emotions, via the amygdala, influence memory formation?

Emotional arousal activates the amygdala, especially the basolateral amygdala, which interacts with stress hormones such as epinephrine and norepinephrine and neuromodulators such as GABA and opioids.
This enhances consolidation in hippocampus and cortex, making emotional events more vivid and long lasting.

How is PTSD related to emotional modulation of memory?

In PTSD, extremely traumatic events trigger intense stress hormone release and strong amygdala activation, causing overly strong consolidation of fear memories.
This leads to intrusive, persistent recollections and hyperarousal because the emotional system has over-stamped the memory.

What is a Hebbian synapse, and what is Hebb’s famous phrase?

A Hebbian synapse is a synapse that increases in strength when the presynaptic and postsynaptic neurons are active together.
Hebb’s famous phrase is “cells that fire together wire together.”

Long Term Potentiation

Long term potentiation is a long lasting, stable increase in synaptic strength that follows a brief, high frequency burst of presynaptic stimulation called a tetanus.

In the hippocampal formation, describe the main pathway involved in classic LTP experiments, the trisynaptic circuit.

Input from entorhinal cortex projects to dentate gyrus via the perforant path.
Dentate gyrus projects to CA3 via mossy fibers.
CA3 projects to CA1 via Schaffer collaterals.
CA1 then projects to subiculum and out through fimbria and fornix back to entorhinal cortex and to mammillary bodies and septum.

At a glutamatergic CA1 synapse, what happens during the induction of LTP involving AMPA and NMDA receptors?

The presynaptic neuron releases glutamate, which activates AMPA receptors causing Na⁺ influx and strong depolarization of the postsynaptic cell.
Depolarization removes Mg²⁺ block from NMDA receptors, so glutamate can open NMDA channels and allow Ca²⁺ influx.
Ca²⁺ activates kinases such as CaMKII and PKC that lead to insertion and phosphorylation of AMPA receptors, making the synapse stronger.

What does CaMKII do during LTP? Give two major effects.

CaMKII increases the number of AMPA receptors in the postsynaptic membrane by trafficking more receptors to the synapse.
It also increases the conductance of existing AMPA receptors so each opening passes more current.
These changes increase the size of EPSPs in response to glutamate.

What is CREB, and what is its role in late LTP?

CREB, the cAMP response element binding protein, is a transcription factor activated by kinases after Ca²⁺ influx.
It turns on genes that produce new proteins such as receptors and structural proteins needed for long term structural changes in synapses and for late LTP and stable memory formation.

What are retrograde messengers in LTP, and what do they do?

Retrograde messengers, such as nitric oxide or carbon monoxide, are small molecules produced in the postsynaptic neuron after Ca²⁺ signaling.
They diffuse back to the presynaptic terminal and increase glutamate release, further strengthening the synapse from the presynaptic side.

Give one piece of evidence that LTP is related to learning and memory.

One example is that blocking NMDA receptors in the hippocampus prevents both LTP and spatial learning in tasks such as the Morris water maze.
Another example is that mice with enhanced NMDA receptor function show stronger LTP and improved learning.

How can artificially activating an engram support the idea that specific cell assemblies store memories?

In mice, neurons in dentate gyrus that were active during fear conditioning were tagged to express channelrhodopsin.
Later, shining blue light in a neutral context to activate just those neurons caused the mouse to show fear as if it remembered the shock context.
This shows that reactivating a specific set of neurons, a cell assembly, is sufficient to re-evoke a memory.

How do astrocytes and oligodendrocytes participate in learning and memory?

Astrocytes modulate synaptic transmission and plasticity, and blocking their signaling can reduce some forms of LTP and learning.
Oligodendrocytes can change myelination in response to learning, altering conduction speed and network timing to support new skill acquisition.

In rodent enrichment studies, how do EC animals differ from IC and SC animals?

Enriched condition animals, housed with social companions and many toys, show thicker cortex, more dendritic branches and spines, enhanced cholinergic activity, and more synapses per neuron, along with better learning performance.
Impoverished condition animals, isolated without stimulation, show the least of these benefits, and standard condition animals are intermediate.

Where does adult neurogenesis mainly occur in the mammalian brain, and what is its relationship to memory?

Adult neurogenesis mainly occurs in the dentate gyrus of the hippocampus and in the olfactory bulb in some species.
New neurons are more plastic and show enhanced LTP, and suppressing neurogenesis impairs certain hippocampal dependent learning tasks such as spatial memory, suggesting these new neurons contribute to memory.

Name two neural changes associated with aging that can impair memory.

Aging can produce loss of synapses and dendritic branches in certain brain regions.
It can also reduce cholinergic projections to hippocampus and cortex and decrease the effectiveness of synaptic plasticity such as LTP, leading to slower processing and weaker memory.