LEARNING AND MEMORY

LEARNING
The behavior of organisms can be separated into three major categories: reflexes, instincts, and
learned behaviors

1) Reflexes: are involuntary responses to stimuli

- produced by prewired neural connections or reflex arcs
- ADVANTAGE: producing rapid, reliable responses
- DISADVANTAGE: inflexibility when the environment changes

2) Instinct: A stereotyped pattern of behavior elicited by particular environmental stimuli.

- mating or parenting behavior
- instinctive behaviors are consistent enough to be referred to as fixed action
patterns.
- Example: Peacock Courtship- the identification of an appropriate female partner
initiates a chain of predictable, stereotyped behaviors. (ibuka sa peacock iyahang
eyes nga feathers something)

3) Learning: A relatively permanent change in behavior or the capacity for behavior due to
experience.
- provides organisms with the most flexible means for responding to the
environment.
- Our definition of learning specifies that only those behavioral changes that result
from experience will be considered learned (excludes changes in behavior that occur
due to maturation or growth.)
- The word “relatively permanent” means the exclusion of brief or unstable
changes in behavior.

TYPES OF LEARNING
Learning occurs in one of two ways:
1) Associative learning: A type of learning that involves the formation of a connection
between two elements or events.
- Example: Classical conditioning

2) Nonassociative Learning: A type of learning that involves a change in the magnitude of

responses to stimuli rather than the formation of connections between elements or
events.
- includes the processes of Habituation and Sensitization

Habituation: A type of learning in which the response to a repeated, harmless stimulus becomes
progressively weaker.

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- You might notice the sound of your air conditioner or furnace turning on or off, yet you
really don’t hear the machine while it’s running

Sensitization: A type of learning in which the experience of one stimulus heightens response to
subsequent stimuli.
- occurs when repeated exposure to a strong stimulus increases response to other
environmental stimuli.
- Example: following major disasters such as earthquakes, people often experience
exaggerated responses to movement, light, and noise.
- Increasing our overall level of responsiveness as a result of detecting one type of harmful
stimulus makes us able to react more quickly to other sources of potential harm

Classical Conditioning: A type of associative learning in which a neutral stimulus acquires the
ability to signal the occurrence of a second, biologically significant event.
● organisms learn that stimuli act as signals that predict the occurrence of other important
events
● Discovered by Russian physiologist Ivan Pavlov (1927)
● Conditioned: refers to the presence of learning
● Unconditioned: refers to factors that are innate or unlearned.
● Conditioned stimulus (CS): In classical conditioning, an initially neutral event that takes
on the ability to signal other biologically significant events.
○ In many of Pavlov’s classic experiments, a ticking metronome served as a conditioned
stimulus
● Unconditioned stimulus (UCS): In classical conditioning, an event that elicits a response
without prior experience.
○ In many of Pavlov’s classic experiments food was used as the unconditioned stimulus.
● Conditioned response (CR): In classical conditioning, a learned reaction to the
conditioned stimulus.
○ Salivating in response to a ticking metronome is a conditioned response because the dog
does this only as a result of experience
● Unconditioned response (UCR): In classical conditioning, a spontaneous unlearned
reaction to a stimulus without prior experience.
○ Salivating in response to the presence of food in the mouth is unconditioned because the
dog does this without prior experience with food
● The development of conditioned responses constitutes the change in behavior that tells
us learning has occurred. Once learning has taken place, the organism not only responds
to the unconditioned stimulus but now responds to stimuli that reliably predict its
arrival.

USING INVERTEBRATES TO STUDY LEARNING

Why are invertebrates used as subjects to study learning?

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- Aside from the fact that they are organisms that are capable of learning, Their
large-celled, simple and hence easily observed nervous systems make them ideal
subjects

Aplysia californica: An invertebrate sea slug frequently used as a subject of experiments on

learning and memory.
Anatomy of Aplysia
● On the Dorsal surface, you can locate the gill
● Mantle Shelf- outer covering of the gill
● Siphon- found at one end of the mantle shelf , a tube through which the animal
releases waste and seawater. (Touching the animal’s siphon reliably produces
Gill-withdrawal reflex)
● Gill-withdrawal reflex: In Aplysia, a protective reflex in which the gill is retracted
in response to touch.

Habituation in Aplysia
● Beginning in the 1960s, Eric Kandel and his colleagues began to trace the neural
pathways responsible for the habituation of the Aplysia gill withdrawal reflex
● Aplysia has neural nets as opposed to brains. Within these neural nets, ganglia, or
collections of cell bodies, serve as major processing centers
● The siphon is served by 24 touch receptors whose cell bodies are located in the animal’s
abdominal ganglion.
● Inside the Aplysia’s abdominal ganglion, there are touch receptors that form synapses
with a number of excitatory and inhibitory interneurons as well as with the six motor
neurons serving the gill.
● Repeated touching of the siphon might produce changes at synapses between the
sensory neurons of the siphon and motor neurons that serve the gill muscles.
● a smaller amount of input to the motor neurons resulted in diminished activity between
the motor neurons and gill muscles, which in turn produced a weak withdrawal reflex.
● Kandel further demonstrated that the reduced activity at the synapse between the
sensory and motor neurons in habituation was a direct result of the release of less
neurotransmitter
● Habituation, even in Aplysia, can last up to three weeks
● long-term habituation probably depends on postsynaptic processes involving the
NMDA glutamate receptor.
● NMDA glutamate receptor has special qualities that allow it to participate in the
structural changes that accompany learning. Chemicals that block glutamate receptors
effectively prevent the development of long term habituation

Sensitization in Aplysia
Overview of the Sensitization Mechanism in Aplysia

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1) Shocking the animal’s tail stimulates sensory neurons, which form excitatory synapses
with a group of interneurons.
2) Interneurons, in turn, form synapses with the sensory neurons serving the siphon
3) The synapses between the interneurons and sensory neurons are axo-axonic in form (the
axon from the interneuron forms a facilitating synapse at the axon terminal of the
sensory neuron)
4) The interneurons release serotonin at these axo-axonic synapses
5) Serotonin binding to sens ory axon terminals inactivates potassium channels.
6) Closure of potassium channels leads to longer action potentials in sensory neurons.
7) Longer action potentials result in increased calcium influx, enhancing neurotransmitter
release
8) The increased release of neurotransmitters produces a stronger response by the motor
neurons and the gill muscles, leading to the stronger gill-withdrawal reflex that we
observe in sensitization.

Structural Changes in Synapses Result from Learning (Habituation and Sensitization)

Bailey and Chen (1983) counted the number
of axon terminals found on sensory neurons
following sensitization and habituation.
Habituation reduced the number of
terminals, whereas sensitization increased
the number of terminals. In animals
undergoing sensitization, the motor neuron
dendrites also showed signs of modification.

● The animals that had undergone sensitization training showed the highest numbers of
terminals, 2,800, compared with 1,300 for the control animals and only 800 in the animals
that had undergone habituation training.
● In sensitized animals, the dendrites of the motor neurons were also modified to
accommodate the increased number of presynaptic elements.
● These structural changes appear to involve actin, a protein that makes up the
microfilaments of the cytoskeleton
● Sensitization involves an increase in the numbers of another type of glutamate receptor,
the AMPA receptor

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Classical Conditioning in Aplysia

Experimental Setup:
● CS+ (Conditioned Stimulus): Slight touch of the mantle shelf.
● UCS (Unconditioned Stimulus): Electrical shock to the tail.
● CS- (Control Stimulus): Occasionally touching the siphon without frequent pairing with
shock.

Conditioning Process
1) Prior to training, touching the mantle shelf produces little if any movement of the gill.
2) After pairings of CS+ (mantle shelf touch) and UCS (tail shock), applying CS+ alone
results in a stronger gill-withdrawal reflex (CR).

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○ In contrast, no changes are observed in the animal’s response to the siphon touch
(CS−), which has never been paired with shock (UCS)
3) The change in the ability of the CS+ to elicit strong gill-withdrawal reflexes meets our
definition of classical conditioning

Mechanism Responsible for Classical Conditioning

● Change in gill-withdrawal reflex correlates with the amount of neurotransmitter
released by sensory neurons onto motor neurons.
● CS+ (mantle shelf touch) induces action potentials in the sensory neuron.
● When these action potentials reach the axon terminal, calcium (Ca2+) enters the cell and
determines the amount of neurotransmitter to be released onto the motor neuron
controlling the gill-withdrawal reflex.
● The shock to the tail (UCS) results in the release of serotonin by an interneuron onto the
sensory axon serving the mantle, closing potassium channels and increasing
neurotransmitter release by the sensory neuron onto the motor neuron.
● Interaction of CS+ and UCS enhances neurotransmitter release by the sensory neuron.
● Similar to habituation and sensitization, postsynaptic mechanisms contribute to
structural changes in classical conditioning.
● Postsynaptic changes involve structural modifications related to neurotransmitter
release.

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CLASSICAL CONDITIONING IN VERTEBRATES

Compared to investigations of invertebrate learning, which prominently feature presynaptic
changes, the emphasis in vertebrate conditioning is on postsynaptic processes such as protein
synthesis in the postsynaptic cells.

Classical Conditioning of Fear

The amygdala plays a very important role in classical
conditioning of emotional responses
● Lesion studies, recording studies, and research
involving the administration of NMDA
antagonists all point to the importance of the
amygdala in this type of learning

Classical Conditioning of Fear in Rats:

● CS (Conditioned Stimulus): Tone.
● UCS (Unconditioned Stimulus): Electrical
shock to the feet.
● CR (Conditioned Response): Reduction in
behaviors incompatible with fear, such as
feeding.
Conditioning Process:
● Pairing of CS (tone) with UCS (shock) results in the tone becoming a
fear-inducing signal.
● CR involves a fear response and inhibition of feeding triggered by the tone alone.
● Information about CS and UCS converges in the amygdala.
● Cells in the amygdala receiving input about both CS and UCS experience a high
influx of calcium.
● Calcium influx triggers a cascade of events, similar to Aplysia, leading to protein
synthesis and increased sensitivity to subsequent CS input.
● When the CS is presented alone, the newly conditioned circuits within the
amygdala respond more strongly than before and are capable of generating the
fear response.

Classical Conditioning of the Eyeblink

Conditioned eye blinks in the rabbit by Richard Thompson and his colleagues
Classical Conditioning Setup:
● CS (Conditioned Stimulus): Tone.
● UCS (Unconditioned Stimulus): Puff of air directed at the rabbit's eye.
● UCR (Unconditioned Response): Movement of the rabbit's nictitating membrane.
○ Nictitating Membrane: An additional, moveable inner eyelid found in
some birds, fish, and mammals but not in humans.

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● CR (Conditioned Response): Tone alone elicits movement of the nictitating

membrane.
Conditioning Process
● a tone (CS) is followed by a puff of air directed at the rabbit’s eye (UCS), which
causes movement of the rabbit’s nictitating membrane (UCR), After several
pairings of the tone and puff, the tone alone will elicit the movement of the
nictitating membrane (CR).
Role of the Cerebellum in Conditioned eye blinks in the rabbit
● evidence points to a role for the cerebellum in this type of classical conditioning
● Thompson and colleagues focus on the interpositus nucleus in the cerebellum.
○ Interpositus nucleus: A cerebellar nucleus thought to be essential to
classical conditioning in vertebrates.
● Recordings from interpositus nucleus cells show an increase in response as
learning progresses.
● Reversible lesion experiments: experiments done to Inactivate the interpositus
nucleus by cooling it which effectively prevents classical conditioning.
○ When the cooling wears off, rabbits begin to learn the conditioned
response as if they had had no prior experience at all.
Role of the red nucleus
● Red Nucleus: a brainstem structure involved in motor control that receives
substantial input from the cerebellum and is directly responsible for performance
of the eyeblink response
● inactivation of the red nucleus by cooling prevents the nictitating-membrane
response
● Learning occurs but is suppressed during red nucleus inactivation; strong
conditioned responses resume upon recovery.
Role of the Cerebellum (Human Studies)
● Human participants do not have nictitating membranes, of course, but they can
learn to blink in response to stimuli paired with a puff of air directed at the eye.
● PET scans in human studies show changes in cerebellar activity during classical
conditioning.
● Individuals with cerebellar damage have a difficult time learning the conditioned
eyeblink response
● Age-related shrinkage of the cerebellum correlates with the speed of acquisition
of conditioned blinking in elderly human volunteers.

Cerebellar Circuits and Classical Conditioning

● Purkinje cell: A cell in the cerebellum that influences its activity by forming inhibitory
synapses with the output cells in the deep cerebellar nuclei.
○ receive inputs known as climbing fibers from neurons located in the inferior olive
in the medulla

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○ Purkinje cells receive input from parallel fibers

○ Integrating input from the parallel and climbing fibers, the Purkinje cells form
inhibitory synapses on the output cells of the cerebellum, located in the deep
cerebellar nuclei.
● Climbing fiber: A fiber originating in the inferior olive of the brainstem that forms
synapses on the large Purkinje cells of the cerebellar cortex.
● Parallel fiber: A fiber originating in the granule cells of the cerebellum that synapses on
the Purkinje cells.
● Granule cell: A cell within the cerebellum that is the source of parallel fibers.
○ Cerebellar granule cells make up possibly half the neurons in the entire brain
○ receives input from mossy fibers
● Mossy fiber (cerebellum): A fiber connecting a neuron in the pons to the granule cells of
the cerebellum.
● Deep cerebellar nuclei: Structures that contain the major output cells of the cerebellum;
recipients of input from the cerebellar Purkinje cells.
● Protein kinase C: A second messenger found in the Purkinje cells of the cerebellum.

James Albus (1971) suggested learning will occur if the climbing fiber and parallel-fiber
synapses onto a Purkinje cell are activated at the same time.
● Masao Ito (1984) provided support for Albus’s predictions.
○ Ito recorded EPSPs in the Purkinje cells in response to electrical stimulation of the
parallel fibers.
○ Simultaneous stimulation of climbing and parallel fibers resulted in a reduction
in Purkinje cell EPSPs lasting up to one hour ( reduced activity in the Purkinje
cells is known as long-term depression,)
■ long-term depression (LTD): A type of synaptic plasticity in which
postsynaptic potentials in target cells are reduced.

Mechanism of LTD
● Reduction in EPSPs is attributed to decreased responsiveness of Purkinje cells to
glutamate released by parallel fibers.
● Activity in climbing and parallel fibers leads to calcium (Ca2+) and sodium (Na+) influx
into the cell.
● Activation of the postsynaptic chemical messenger, protein kinase C, occurs
simultaneously.
● These events collectively decrease the number of available glutamate receptors in the
Purkinje cell membrane.
● Fewer receptors result in reduced EPSPs during subsequent input, leading to LTD.

Trace Conditioning and Extinction

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Delay conditioning: A type of classical conditioning in which CS onset precedes and overlaps
UCS onset.
● Type of conditioning in Aplysia, rabbits and Humans

Trace conditioning: A type of classical conditioning in which the CS and UCS do not overlap in
time.

Different Learning Processes in Delay and Trace Conditioning

● Research with mutant mice revealed abnormal cerebellums, affecting delay conditioning
but not trace conditioning.
● human patients with cerebellar lesions showed greater impairment in delay than in trace
conditioning
● bridging the time gap between the CS and UCS in trace conditioning requires the
participation of forebrain areas, including areas of sensory cortex, the hippocampus, and
the prefrontal cortex
● Unlike direct projection in delay conditioning, trace conditioning requires forebrain
structures to hold CS information during the stimulus-free interval.

Memory

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MEMORY
TYPES OF MEMORY
Information processing models : theories of memory that seek to explain the management of
information by the brain, from detection to storage to retrieval
● assume that information flows through a series of stages on its way to permanent
storage in memory

Atkinson-Shiffrin Model of Memory

1) Sensory memory: An initial stage in memory formation in which large amounts of data
can be held for very short periods.
2) Short-term memory (“working” memory) :An intermediate memory store in which
limited amounts of data can be held for a limited amount of time; without further
processing, such information is permanently lost.
○ Information in short-term memory is sorted into temporary storage areas or
buffers for auditory, visual, or combined types of information, which are
managed by a “central executive” process
3) long-term memory: A memory store in which apparently unlimited amounts of data can
be held for an unlimited amount of time.
○ Semantic memory: A type of declarative, explicit memory for facts and verbal
information.
■ “Who was the first president of the United States?” or “What is a bagel?”
○ episodic memory: A type of declarative, explicit memory for personal experience.
■ to remember the episodes of your life—what you ate for breakfast or the
time you chose your first puppy.
○ procedural memory: A type of implicit memory for performing learned skills and
tasks.
■ riding a bicycle, using a software program, or cooking your favorite meal

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● Semantic and episodic memories are grouped together as declarative memories. . These
types of memories are declarative in the sense that they can easily be described in words,
or “declared.” In contrast, procedural memories are often quite difficult to describe
verbally but are easy to demonstrate or perform
● Declarative memories are typically recalled consciously or explicitly, whereas procedural
memories are usually recalled unconsciously or implicitly.
● classical conditioning, habituation, and sensitization are also considered examples of
nondeclarative or implicit processes.
○ However, trace conditioning shares many similarities with declarative memory.

Anterograde amnesia: Memory loss for information processed following damage to the brain.
● patients have good recall for events that occurred prior to the time of their brain
damage, but they seem unable to remember anything they experience following their
brain damage
● patients with anterograde amnesia were able to learn to solve the Tower of Hanoi puzzle
(When asked about the puzzle, most patients could not recall seeing it before, and they certainly
had no confidence that they could solve it)
○ their brain damage did not prevent them from forming implicit memories of how
to solve the puzzle, although it did prevent them from explicitly remembering
that they knew how to solve it
● Engram: A physical memory trace in the brain.

BRAIN MECHANISMS IN MEMORY

Early Efforts to Locate Memory Functions
Karl Lashley Observed the Results of Brain Lesions on Maze-Learning Performance
● Karl Lashley- one of the earliest psychologists to tackle the problem of locating the
engram. reasoned that the engram might be located in the association cortex, areas of
cortex that are not locked into a specific sensory or motor function.
● Lashley performed a series of lesions on rats both before and after they were trained to
run through mazes to find food.

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○ Rats that received cortical lesions prior to any training were slow to learn their
way through the maze.
○ Rats that received cortical lesions following their training seemed to have
forgotten many of their previously learned behaviors.
● larger lesions appeared to produce poorer performance, regardless of where the lesion
was made
○ Lashley mistakenly concluded that all parts of the cortex make an equal
contribution to learning and memory, a concept he referred to as equipotentiality.
○ the more cortex you have, the better your memory will be, a concept Lashley
referred to as mass action.
Why is Lashley’s conclusion believed to be a mistake?
- Recent data suggest that all parts of the cortex are not equally likely to participate
in memory.
- Lashley’s lesions were huge
- maze learning is a complex task involving a number of sensory and motor
processes.
● Lashley’s major contribution was his suggestion that memories are in fact distributed
across the cortex rather than stored in one specific location. This conclusion stimulated
further efforts to identify areas of the brain responsible for storing memory.

The Temporal Lobe and Memory

● Significant evidence of the temporal lobe’s involvement in memory came from case
studies of patients with anterograde amnesia.
○ patients suffering from anterograde amnesia appear to retain their newly
acquired procedural, implicit memories while experiencing a dramatic deficit in
their ability to form new explicit memories

Surgical Removal of Temporal Lobe Tissue in Patient H. M.

● As a result of a childhood bicycle accident in which he suffered brain damage, H. M.
experienced severe seizures that required extensive surgery when he was 27
● the hippocampus, amygdala, and part of the association cortex of the temporal lobe were
removed from both his right and left hemispheres
● The good news for H. M. was that his seizure disorder was much improved and his
personality, vocabulary, and above-average IQ appeared unchanged
● He remembered most of the information he had acquired prior to surgery, but his
anterograde amnesia was profound.
○ He seemed completely unable to transfer any new information about people,
places, events, and numbers from short-term memory to long-term memory.
● Damage to the medial temporal lobes, such as in the case of H. M., affects explicit but
not implicit memories.

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Delayed nonmatching to sample (DNMS) task: A standard test of memory in which the subject
must identify the novel member of a stimulus pair following a delay.
● To find food successfully, monkeys must select the non matching (new) stimulus
following a delay.
● Monkeys with medial temporal lobe damage appear to have difficulty forming new
memories and subsequently perform poorly on the task.

Structures typically damaged by medial temporal lobe lesions include the amygdala, the
hippocampus, and the surrounding areas of cortex known as the parahippocampal cortex and
the rhinal cortex.
● Parahippocampal cortex: An area of cortex just ventral to the hippocampus.
● Rhinal cortex: An area of cortex ventral to the hippocampus.

Long-Term Potentiation (LTP)

Major anatomical features of the hippocampus and surrounding structures
● The hippocampus consists of a gentle arc just medial to the lateral ventricle in each
hemisphere.
● Ventral to the hippocampus are the parahippocampal cortex and rhinal cortex
(entorhinal and perirhinal cortices).
○ entorhinal cortex: A subdivision of the rhinal cortex, which lies ventral to the
hippocampus.
○ Perirhinal cortex: A substructure of the rhinal cortex.

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● Association areas of the cortex provide input to parahippocampal and rhinal cortices,
which transmit information to the hippocampus.
● Output from the hippocampus travels along the fornix, a pathway that terminates in the
hypothalamus
○ Fornix: A pathway carrying information from the hippocampus to the
hypothalamus.
● Hippocampus has two main layers: Ammon's horn and dentate gyrus.
○ Ammon’s horn: One of two major layers of neurons found in the hippocampus.
■ further divided into four sections, named CA1 to CA4. (CA stands for the
Latin term for Ammon’s horn, cornu Ammonis.)
○ Dentate gyrus: One of two major layers of neurons found in the hippocampus.

Hippocampal Pathways
1) Input from the rhinal cortex travels along the perforant pathway, whose axons form
synapses on the cells of the dentate gyrus.
○ Perforant pathway: A pathway made up of axons originating in the rhinal cortex
that form synapses in the dentate gyrus of the hippocampus.
2) Axons from the dentate gyrus, also known as mossy fibers, synapse on cells found in
CA3
○ mossy fiber (hippocampus): An axon from the dentate gyrus that synapses on
cells found in CA3 of Ammon’s horn.
3) Axons from CA3 form two branches. One branch, the Schaffer collateral pathway,
synapses with the cells of CA1. The other branch exits the hippocampus as the fornix.
○ Schaffer collateral pathway A pathway connecting CA3 to CA1 in Ammon’s horn
of the hippocampus.

Long-Term Potentiation (LTP): A type of synaptic plasticity in which the application of a rapid
series of electrical shocks to an input pathway increases the postsynaptic potentials recorded in
target neurons.
● Bliss and Lømo (1973) demonstrated that a rapid series of electrical shocks (50-100
stimuli at 100 stimuli per second) increase postsynaptic potentials in target hippocampal
cells.
● LTP is a change in responsiveness in target cells after a rapid series of shocks.
● LTP can last indefinitely in living animals and several hours in brain slices.
● importance of LTP in Memory
1) LTP lasts a long time
2) takes only seconds of input to produce
3) Fits the cellular learning model proposed by Donald Hebb in 1949, emphasizing
associativity and cooperativity.
■ associativity: A condition believed necessary for learning in which the
pre- and postsynaptic neurons are nearly simultaneously active.

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■ cooperativity: A condition for the formation of LTP in which several

synapses onto the target postsynaptic neuron must be simultaneously
active.
● LTP Mechanism with NMDA Receptors:
○ NMDA receptors require simultaneous activity of both pre- and postsynaptic
neurons.
○ The channel of the NMDA receptor is blocked by Mg2+, which is expelled upon
depolarization of the postsynaptic cell.
○ Depolarization typically requires activity from other synapses onto the same
postsynaptic neuron (cooperativity).
○ Binding of glutamate to unblocked NMDA receptors allows entry of Na+ and
Ca2+, stimulating second messengers and initiating structural changes to
strengthen the synapse.
○ LTP is a general process of learning implemented by various receptors and
signaling systems.
○ Presynaptic and postsynaptic processes are important in different locations.
○ LTP occurs with or without the neurotransmitter glutamate.

LTP and Spatial Memory

● Studies of spatial memory, or an organism’s ability to map a location, provide further
evidence linking LTP to memory

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○ Joe Tsien and his colleagues (Tsien, Huerta, & Tonegawa, 1996) reported that
knocking out the gene that encodes a component of the NMDA receptor found in
the cells of CA1 has a negative impact on LTP in the Schaffer collateral pathway.
○ LTP is also negatively affected when genetic mutations affect the second
messengers in CA1 cells
● Animals with impaired LTP can still form spatial maps. However, impaired LTP
prevents the animals from forming stable, well-defined maps.
○ A mouse with impaired LTP returns to a familiar place, it forms a new map
instead of reactivating a previous one. (acts a lot like patient H. M., who is unable to
learn the route to his post surgery home.)
● Spatial learning in rodents can also be impaired by the application of NMDA receptor
antagonists
○ When these chemicals are applied to the hippocampus in rats, the rats are unable
to learn the location of an underwater platform in the Morris water-maze
○ prevent the development of LTP in the hippocampus of these rats

The Diencephalon and Memory

● The hippocampus and other Areas of the temporal lobe are tightly connected to the
thalamus. Disruption to these structures or to their connections appears to result in
amnesia
Damage to the Diencephalon in Patient N. A.
● Patient N. A. suffered brain damage as a result of a freak accident in which he
was stabbed through the nostril with a fencing foil (a long thin metal blade) held
by one of his roommates.
● N. A. suffered a lesion in his left dorsomedial thalamus
● Patient N. A. experienced significant anterograde amnesia as well as some
retrograde amnesia, affecting memories from several years prior to his accident
● N. A. was quite similar to that of H. M. His intelligence and short-term memory
were preserved, but he had difficulties forming new declarative (explicit)
memories.

Korsakoff’s syndrome: Anterograde amnesia resulting from thiamine deficiency, typically found
in chronic alcoholics.
● Chronic alcoholics who develop Korsakoff’s syndrome experience anterograde amnesia
similar to that of patients H. M. and N. A.
● Untreated thiamine deficiencies lead to damage in the dorsomedial thalamus and
mammillary bodies of the diencephalon
● patients with Korsakoff’s syndrome usually experience severe retrograde amnesia,
possibly due to lesions in the cerebellum, brainstem, and cortex as well as in the
diencephalon.

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Semantic Memory and the Cerebral Cortex

● There appears to be considerable evidence that semantic knowledge, or our basic
knowledge of facts and language, is widely distributed in the cortex.
● Alex Martin and his colleagues (Martin, Wiggs, Ungerleider, & Haxby, 1996) used PET
scans to identify brain areas that participants activated while naming either animals or
tools
○ while naming animals– participants activated their left medial occipital lobes
(part of the brain responsible for visual input)
○ while naming tools– the participants activated the left premotor area and the left
middle temporal gyrus (areas that are associated with concepts related to tool
use, such as hand movements and the production of action words)
● Antonio Damasio suggests that this type of coordination might occur in a “convergence
zone,” or a particular location responsible for assembling separate aspects of a memory
into a whole.
○ most likely candidate is left lateral inferior frontal gyrus

Episodic Memory and the Cerebral Cortex

Patients who experience damage to the prefrontal areas of the cortex often experience a memory
deficit known as source amnesia. (Memory loss for the circumstances in which a particular fact
or skill was learned.)
● These patients retain their semantic memories but are unable to remember how and
when they learned a bit of information

Episodic memories are essential to our sense of self, leading to the intriguing notion that we
might be able to locate a sense of “self” in the brain.
● Imaging studies indicate that the anterior prefrontal cortex and the posterior cingulate
cortex participate in the retrieval of personal, episodic memories

We might use our episodic memories to distinguish between fantasy and reality.
● When considering reality, structures associated with episodic memory, such as the
prefrontal cortex and posterior cingulate cortex, were active.
● when considering fantasy, areas associated with semantic processing, such as the left
inferior frontal gyrus (IFG) showed greater activity
○ Disturbances in this distinction might form the basis for the delusions, or false
beliefs, that characterize some psychological disorders

Short-Term Memory and the Brain

● Baddeley (1974, 2000) further divided short-term memory, or working memory, into four
components: a central executive, the phonological loop, the visuospatial scratchpad, and
an episodic buffer.

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● The dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) are
believed to provide the neural basis for the central executive
● Human patients with prefrontal cortex lesions have significant difficulty with the
Wisconsin card-sorting test
○ Patients with prefrontal lesions can learn a sorting rule—for example, “put all the
cards with the same-colored objects together”—but they can’t seem to adjust
when the rule changes.
● A certain level of maturity in the prefrontal cortex is necessary for short-term memory.
● Evidence for an executive role for the anterior cingulate cortex (ACC) in shortterm
memory comes from comparisons of people with large or small short-term memory
capacities for verbal information
○ People with large capacities show more activation of the ACC than people with
smaller capacities
○ . People with smaller capacities used rehearsal, or simple repetition, to maintain
information in short-term memory, whereas people with larger capacities were
more likely to use semantic strategies, such as imagery and making stories

The Striatum and Procedural Memory

● The striatum, including the basal ganglia and nucleus accumbens, are involved with the
formation of procedural memories
○ basal ganglia are part of our motor system, involved in the learning and memory
of motor patterns
○ nucleus accumbens contributes an evaluation of emotion and reward to the
learning of procedures
● The role of the striatum in procedural, but not declarative, memories was demonstrated
by observing the effects of lesions on rats trained in one of two different maze tasks
○ Lesions to structures associated with the hippocampus impaired performance on
the declarative task (the standard maze), but performance on the procedural task
(the light maze) remained normal.
○ However, rats with lesions in the basal ganglia performed poorly on the
procedural task but experienced little difficulty with the declarative task.

BIOCHEMICAL FACTORS IN LONG-TERM MEMORY

● The binding of serotonin by the sensory neuron activates an enzyme, adenylyl cyclase,
which in turn converts adenosine triphosphate (ATP) into the second messenger, cyclic
AMP (cAMP).
○ Cyclic AMP (cAMP): A second messenger that participates in processes such as
changes that occur as a result of learning and the responses of photoreceptors to
light.

● cAMP activates protein kinase A (PKA)

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○ Protein kinase A (PKA): An enzyme capable of modifying proteins responsible

for structural change in the axon terminal.
1) PKA decreases the potassium (K+) current, which prolongs the action
potential. As a result of the prolonged action potential, more calcium
(Ca2+) enters the axon terminal;
2) PKA also signals the movement of more vesicles into the release zone;
and
3) PKA opens more Ca2+ channels. These processes result in the enhanced
release of glutamate by the sensory neuron.
● The sequence leading to long-term changes in behavior and protein synthesis is known
as the cAMP-PKA-MAPK-CREB pathway
○ These processes take up where the short-term modification left off, with the
activation of PKA.
● When PKA is recurrently activated,
as it is in repeated sensitization
training, it activates another second
messenger, mitogen- activated
protein (MAP) kinase.
○ Mitogen-activated protein
(MAP) kinase: A second
messenger that responds to
extracellular stimuli by
initiating intracellular
processes such as gene
expression and apoptosis.
● PKA and MAP kinase are
transported back from the axon
terminal to the neural cell body,
where together they activate a
genetic switch in the cell nucleus.
The switch is a protein known as
CREB-1 (for cAMP response element
binding protein).
○ CREB-1: A protein that
activates genes that might be
responsible for structural
changes associated with
long-term memory.
● the two kinases (MAP and CREB-1) block the inhibitory actions of CREB-2
○ CREB-2: A protein that normally inhibits the transcription of genes associated
with structural changes in long-term memory.

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● Activating CREB-1 and inhibiting CREB-2 causes two important genes to be expressed.
1) ubiquitin carboxyterminal hydrolase: An enzyme that allows PKA to be rather
continuously active, possibly contributing to long-term memory.
2) C/EBP: A substance activated by CREB-1 that in turn activates genes related to
synaptic growth.
● Biochemical pathways of learning can be modified through genetic manipulation.
○ The fruit fly, Drosophila, is capable of classical conditioning.
■ Different genetic variants of Drosophila were identified as having serious
deficits in learning the odor-shock association.
■ Researchers have named these impaired flies (and the genes responsible
for their impairment) radish, turnip, dunce, rutabaga, amnesiac, and, less
creatively, PKA-R1
■ When the action of PKA was blocked in the flies, the flies were unable to
learn and form short-term memories.
■ too much CREB-2 blocks flies’ long-term memory but not short-term
memory.
■ extra CREB-1 produces immediate long-term memory under conditions
that normally would produce only short-term retention

THE EFFECTS OF STRESS ON MEMORY

The experience of trauma is widely believed to influence memory.
● Freud believed that traumatic memories can become so inaccessible that they are
essentially lost or repressed.
● memories of trauma in posttraumatic stress disorder (PTSD) are often unusually vivid
and intrusive

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● Flashbulb memories for traumatic events seem to be recalled with unique precision

Yerkes-Dodson Law
● According to the Yerkes-Dodson Law, stress effects on memory interact with the
complexity of a task.
○ If the task is simple, such as asking a mouse to avoid shock (the stressor) by
choosing a light or dark escape box, performance of the task will improve in a
linear fashion with increasing stress
○ When tasks are more complicated, such as asking the mouse to choose between
two escape boxes with equal levels of illumination, performance is no longer
linear. (performance increases as stress increases to a certain point and then
decreases with stronger stress)
○ These interactions between stress levels and tasks are critical to understanding
repression, posttraumatic memories, and flashbulb memories.
● Diamond et al. (2007) argue that the onset of stress initially enhances memory formation,
as in the case of traumatic and flashbulb memories.
○ followed by a refractory period of hours or even days, during which the ability to
form new memories is impaired.
● What would be the advantages of this period of relatively impaired memory formation?
○ continued stimulation of the hippocampus due to stress could be toxic to
hippocampal neurons
○ emotional events often have survival implications, and a refractory period might
serve to protect memories for these important events from the interference
produced by new learning or the modifications observed by Loftus
● Activity of the hippocampus during stressful events is accompanied by parallel,
independent LTP in the amygdala.
○ LTP in the amygdala is enhanced immediately following the onset of stress but
later experiences a refractory period
● In addition to its impact on the hippocampus and amygdala, stress affects the functions
normally carried out by the prefrontal cortex, including coping skills, decision making,
planning, and multitasking.
○ inverted U-shaped relationship between performance of complex tasks, stress,
and the accompanying release of dopamine and norepinephrine in the prefrontal
cortex is consistent with the Yerkes-Dodson Law
● Higher levels of cortisol are correlated with the reporting of more false memories
● Propanolol, which blocks the effects of glucocorticoids in the brain, might prevent the
formation of traumatic memories when administered immediately following a traumatic
event
● By manipulating certain enzymes in animals, researchers are making progress in their
ability to “erase” some long-term memories, raising the possibility of new approaches to
the treatment of PTSD

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AGING AND MEMORY

● Some aspects of learning and memory undergo age-related changes, even in healthy
older adults
● eyeblink conditioning is more difficult and takes longer in older participants
● As people age, decreased blood flow is observed in many parts of the brain essential to
memory and cognition, especially in the frontal and temporal lobes.
● However, the aging brain also shows areas of increased activation.
○ Beason-Held et al. (2008) suggest that these areas of increased activity represent a
reorganization of the brain that allows cognitive performance to remain stable in
spite of age-related deficits in brain function.
● No differences in hippocampal activation during the encoding of face-name pairs
between young and older adults.
● Successful recall demonstrated in both age groups.
● young participants show reduced activation of the parietal lobe and the posterior
cingulate cortex during successful encoding
● Participants at risk for Alzheimer’s disease, either because of their genetic vulnerability
or evidence of mild cognitive impairment, actually demonstrate increased hippocampal
activity during encoding compared to healthy older participants.
○ Eventually, this compensation fails as dementia progresses, and activity in the
hippocampus is reduced below that seen in healthy older controls

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