Learning and memory by HC120229063711


									Learning and memory
Behavior is the result of the interaction between genes and the environment.
How the environment influences behavior --- learning and memory
1. What is the major form of learning?
2. What types of information about the environment are learned most easily?
3. Do different types of learning give rise to different memory processes?
4. How is memory stored and retrieved?

Memory can be classified as implicit or explicit on the basis of how information
is stored and recalled
1861 Broca --- find Broca’s area (a mental related functional area)
the middle of 20th century psychologists doubted that memory was a discrete function, independent of
perception, language, or movement. (Lashley study)
the beginning of 20th century Chales Sherrington --- mapping the motor representation of anesthetized
1940s Wilder Penfield --- memory processes might be localized to specific regions of the human brain.
Stimulating temporal lobe produced an experiential response.
mid 1950s Brenda Milner (worked on patients with bilateral removal of the hippocampus and
neighboring temporal lobe) (H.M. case) <<Fig. 62-1>><<Fig. 62-2>>
--- good procedural memory and long-term memory; unable to transfer new short-term memory into
long-term memory.
amnesia --- memory deficit

The distribution between explicit and implicit memory was first revealed with lesions of the
limbic association areas of the temporal lobe<<Fig. 62-3>><<Fig. 62-4>>
Implicit memory (nondeclarative memory) --- priming, procedural, associative learning (classical &
operant conditioning), nonassociating learning.
Explicit memory (declarative memory) --- episodic & semantic memory

Animal studies help to understanding memory<<Fig. 62-5>>
The processing information for explicit memory storage in entorhinal cortex
1. the main input to the hippocampus
2. the major output of the hippocampus.

Damage restricted to specific subregions of the hippocampus is sufficient to impair explicit
memory storage
The hippocampus may be relatively more important for spatial representation.
Lesions of the right hippocampus give rise to problems with spatial orientation; lesions of the left
hippocampus give rise to defects in verbal memory. <<Fig. 62-6>>

Explicit memory is stored in different association cortices
Patients with amnesia are able to remember their childhood, the lives, and the factual knowledge they
required before damage to the hippocampus (anterograde amnesia) --- the hippocampus is only a
temporary way station for long-term memory. It would then slowly transfer information into the
neocortical storage system.
Explicit memory depends on conscious experience.

Semantic (factual) knowledge is stored in a distributed fashion in the neocortex
Associative visual agnosia --- damage to the posterior parietal cortex (patient can identify objects and
reproduce detailing drawing) <<Fig. 62-7>>
Apperceptive visual agnosia --- damage to the occipital lobes and surrounding region (unable to draw
object but can name it)
Prosopagnosia --- lesions in the inferotemporal cortex (unable to recognize familiar faces or learn new
faces, but leave intact all other aspects of visual recognition)
Category-specific defect:<<Fig. 62-8>>
Naming of animal & tools --- bilateral activation of the ventral temporal lobe and Broca’s area.
Naming animals --- selectively activated the left medial temporal lobe involved in earlier stage of
visual image.
Naming tools --- selectively activated a left premotor area and left middle temporal gyrus.

Episodic (autobiographical) knowledge about time and place seems to involve the prefrontal

Explicit knowledge involves at least four distinct processes
Three important things about episodic and semantic knowledge:
1. there is not a single, all-purpose memory store.
2. any item of knowledge has multiple representations in the brain.
3. both semantic and episodic knowledge are the results of at least 4 related but distinct types of
  processing: encoding, consolidation, storage, and retrieval.<<Fig. 62-9>>

Working memory is a short-term memory required for both the encoding and recall of explicit
Working memory: a special short-term memory store.
An attentional control system is located in the prefrontal cortex. The attentional control system
regulated the information flow to 2 rehearsal systems, then working memory system could enter
long-term memory.
Articulatory loop --- memory for words and numbers can be maintained by subvocal speech.
Visuospatial sketch pad --- store the visual properties and the spatial location of objects.

Implicit memory is stored in perceptual, motor, and emotional circuit
Implicit memory does not depend on conscious process. This type of memory builds up slowly, and is
expressed primarily in performance, not in words.
Fear conditioning --- amygdala; operant conditioning --- striatum & cerebellum; classical conditioning,
sensitization & habituation --- sensory and motor systems.<<Fig. 62-4>>

Implicit memory can be nonassociative or associative
2 forms of nonassociative learning: sensitization & habituation.
Dishabituation: a sensitized stimulus can override the effects of habituation.

Classical conditioning involves associating two stimuli <<Fig. 62-10>>
Since Aristotle, western philosophers have thought that learning is achieved through the association of
Ivan Pavlov introduce into the study of learning on classical conditioning.
Conditioned stimulus (CS) vs. unconditional stimulus (US)
If US is rewarded (food or water), the conditioning is appetitive; if the US is noxious, the conditioning
is defensive.
The capacity for CS to produce a classically conditional response is not function of the number of times
the CS is paired with an US but rather the degree to which the CS and US are correlated.
Classical conditioning is the responsiveness of specific reflex responses to selected stimuli.
Extinction is an important adaptive mechanism.

Operant conditioning involves associating a specific behavior with a reinforcing event
Edgar Thorndike, B.F, Skinner --- operant conditioning (trial-and-error learning)

Timing is critical in both forms of conditioning. Predictive relationships are equally important in both
types of learning.
Two forms of learning may use the same neural mechanisms.

Associative learning is not random but is constrained by the biology of the organism
Not all reinforces are equally effective with all stimuli or all responses.
Bait shyness, food-aversion conditioning (vanilla vs. nausea)
An animal will not develop an aversion to a distinctive visual or auditory stimulus that has been paired
with nausea.

Certain forms of implicit memory involve the cerebellum and amygdala
Protective eyeblink reflex (a specific form of motor learning) in rabbits.
damage to the vermis and the interpositus nucleus of the cerebellum abolishes the conditioning
response, but does not affect the unconditioning response.
Cerebellum is involved vestibulo-occular reflex (keeping the visual image fixed by moving the eyes
when head moves)

Some learned behaviors involve both implicit and explicit form of memory

Both explicit and implicit memory are stored in stages<<Fig. 62-11>>
Retrograde amnesia vs. anterograde amnesia
Recent memories are more susceptible than older memories to disruption by electroconvulsive therapy
An overall view
The neurobiological study of memory has yielded 3 generalizations:
         Memory has stages; long-term memory is represented in multiple regions; explicit and implicit
memories involve different neuronal circuits.
Long-term explicit memory requires temporal lobe; implicit memory involves cerebellum, amygdala
and specific sensory & motor system.
Memory involves both functional and structural changes at synapses.

Cellular mechanisms of learning
Short-term storage of implicit memory for simple forms of learning results from
changes in the effectiveness of synaptic transmission

Habituation involves an activity-dependent presynaptic depression of synaptic transmission
Habituation was first investigated Ivan Pavlov and Charles Sherrington in certain reflexes.
Alden Spencer and Richard Thompson investigated at cellular level in leg withdraw reflex.
Aplysia (containg only ~2000 central nerve cells) has a repertory of defensive reflexes (gill withdraw)
for withdrawing its gill and its siphon. <<Fig. 63-1>><<Fig. 63-2>>
Quantal analysis revealed a decrease in number of transmitter (glutamate) vesicles released from
presynaptic terminals of sensory neurons. No change in the sensitivity of NMDA & non-NMDA
receptors with habituation. --- due to in part to a reduced mobilization of transmitter vesicles to the
active zone. Local inhibitory interneuronl circuitry.
Spaced training is usually much more effective than massed training in producing long-term memory.

Sensitization involves presynaptic facilitation of synaptic transmission<<Fig. 63-3>>
Aplysia --- serotonin release & axoaxonic synapses on the presynaptic terminals.
Serotonin – GTP binding protein (Gs) – Gs activated adenylyl cyclase --- produce cAMP – activate
cAMP-depedent PKA – 1. close K+ channel; 2. increase mobile of vesicle; 3. open L-type Ca2+ channel.
Serotonin – GTP binding protein (Go) – Go activated PLC --- via Diacylglycerol reaction – activate
PKC –1. increase mobile of vesicle; 2. open L-type Ca2+ channel.

Classical conditioning involves presynaptic facilitation of synaptic transmission that is dependent
on activity in both the presynaptic and the postsynaptic cell<<Fig. 63-4>><<Fig.63-10>>
Interstimulus interval between CS & US is ~0.5s in Aplysia study.
Classical conditioning involves activity-dependent facilitation at both pre- & post-synaptic components
Each action potential activate Ca2+-binding protein calmodulin -- Ca2+/calmodulin binds to adenylyl
cyclase – potentiating serotonin response & enhancing cAMP production.

Long-term storage of implicit memory for sensitization and classical
conditioning involves the cAMP-PKA-MAPK-CREB pathway

Molecular biological analysis of long-term sensitization reveals a role for cAMP signaling in
long-term memory<<Fig. 63-5>><<Fig.63-6>>
Repeated experience consolidates memory by converting the short-term form into a long-term form.
Similarity between short-term memory & long-term memory:
1. changes in the strength of components at several synaptic sites.
2. enhanced release of transmitter.
3. converting short-term form into long-term form by repeated exposure.
4. intracellular 2nd messenger pathways (cAMP & PKA) are involved in both short-term & long-term.
Short-term & long-term memory shows distinct processes in epileptic patient study and inhibiting
protein or mRNA synthesis study.
CREB-1 & CREB-2 in PKA system; C/EBP in growth of new synaptic connections.
Structural changes in presynaptic terminals of sensory neurons.

Genetic analysis of implicit memory storage for classical conditioning also implicate the
cAMP-PKA-CREB pathway
Four mutants of Drosophila fail to show sensitization & have a defect in the cAMP.
Dunce: lacks phosphodiesterase (an enzyme that degrades cAMP)
Rutabaga: defective in the Ca2+/calmodulin-dependent adenylyl cyclase.
Amnesiac: lack a peptide transmitter that acts on adenylyl cyclase.
PKA-R1: defective in PKA.

Explicit memory is mammals involves long-term potentiation in the
Three major pathways of the hippocampus:<<Fig.63-7>>
1. perforant pathway: from entorhinal cortex to granule cells of the dentate gyrus.
2. mossy fiber pathway: from granule cells to pyramidal cells in the CA3 of the hippocampus.
3. Schaffer collateral pathway: excitatory collaterals of pyramidal cells in CA3 to pyramidal cells in
Per Andersen showed the hippocampus has 3 major pathways.
1973 Timothy Bliss & Terje Lomø --- each of these pathways is remarkably sensitive to the history of
previous activity (long-term potentiation, LTP).

Long-term potentiation in the mossy fiber pathway is nonassociative<<Fig. 63-8>>
After titanic stimulation – rise Ca2+ inflow – activate Ca2+/calmodulin-dependent adenylyl cyclase

Long-term potentiation in the Schaffer collateral and preforant pathways is associative<<Fig.
63-7>><<Fig. 63-9>><<Fig.63-10>><<Fig. 63-11>>
Cooperativity (NMDA receptor-channel) --- required activation of several afferent axons.
Associativity (Hebb’s rule) --- simultaneous firing in both the postsynaptic and presynaptic neurons
The release of glutamate is enhanced during LTP; the probability of transmitter release increases during
LTP by quantal analysis. Retrograde messengers (NO) involves in LTP.

Long-term potentiation has a transient early and a consolidated late phase<<Fig. 63-12>><<Fig.

Genetic interference with long-term potentiation is reflected in the properties of place cell in the
hippocampus<<Fig. 63-14>><<Fig. 63-17>>
1971 John O’Keefe and John Dostrovsky discovery that the hippocampus contains a cognitive map
(place field) of the spatial environment in which an animal moves. (Spatial memory)
Place cell in the hippocampus --- encoding a position in space.
Associative long-term potentiation is important for spatial memory<<Fig.63-17>><<Fig.63-18>>

Is there a molecular alphabet for learning?
Changes in the somatotopic map produced by learning may contribute to the
biological experience of individuality

Neuronal changes associated with learning provide insights into psychiatric


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