Learning and Memory. Learning relatively permanent change in behavior as a function of training, practice or experience excludes behavioral changes resulting

Learning and MemoryLearning and Memory


Learning

relatively permanent change in behavior as a function of training, practice or experience

excludes behavioral changes resulting from sensory adaptation or fatigue

memory is implicit in the definition of learning

“relatively permanent” implies a lasting alteration of nervous system structure and/or function


Two aspects of learning

1. acquisition of a response in presence of a stimulus

2. suppression of responses in its absence

Two fundamental questions

1. What are the neural mechanisms of learning? (cellular level)

2. What is learned? (where in the brain; organizational level)

To answer the first question, simplified systems have been studied.•Simple forms of learning

•Simple systemse.g. invertebrates, simplified mammalian preparations

• Non-associative– Habituation, sensitization– perceptual in nature– recognition of objects and situations

• Associative– Classical conditioning

• S-S learning

– Operant Conditioning• R-S learning

Types of Learning

Associative learning may involve

• acquisition of new motor behaviors

• acquisition of associations between new stimuli and existing behaviors

• acquisition of new associations between familiar stimuli and existing responses.

Non-associative learning

habituation• repeated exposure to a stimulus results in

reduced responding to that stimulus• generally neutral, non-noxious stimuli

sensitization• repeated exposure to a stimulus results in

increased responding to that stimulus• generally biologically relevant, strong hedonic

valence (+ or -)• also refers to augmentation of responding

following exposure to a second stimulus

Associative learning

classical conditioning; Pavlovian conditioning; respondent conditioning•A neutral stimulus is paired with a stimulus that reliably elicits a response. Conditioning is indicated when the previously neutral stimulus elicits a response.

CSUSUR

US

CS

URCRCR

Associative learning

operant conditioning; instrumental learning•repeated presentation of a stimulus after emission of a designated response increases (reinforces) or decreases (punishes) the likelihood of that response

CRUSUR

Modeling, latent learning

Usually defined as learning in the absence of a reinforcer (US or conditioned reinforcer such as money)

Problem: One can always posit a “hidden reinforcer,” a negative hypothesis that cannot be disproven. The burden of proof therefore falls on those to make hidden reinforcers evident.

The existence of mirror neurons seems to provide a neurobiological basis for imitative learning.

Eric Kandel and his collaborators used Aplysiato unravel synapticmechanisms for short- andlong-term habituation, short- and long-term sensitization, and classicalconditioning.

Eric Kandel won the 2000 Nobel Prize for Physiology and Medicine for this work.

Research on neural mechanisms has focused on non-associative learning and classical conditioning.

Aplysia

Habituation in Aplysia

Sensitization in Aplysia

Kandel termed the neural mechanisms that underlie behavioral sensitization,“heterosynaptic facilitation,” which is produced by a second (usually strong) stimulus

heterosynapticfacilitation

5-HT released ontopresynaptic terminal(metabotropic synapse)

c-AMP mediated closureof K+ channels

Prolongation of depolarization at the terminal

greater Ca2+ influx

more neurotransmitter released onto target neuron

Memory in Aplysia also involves structural changes in the presynaptic terminal

group active zones active zone area

vesicles/active zone

vesicles/neuron

naïve 100% .16 um 13 2250

habituated 28 .11 4 500

sensitized 183 .28 20 6300

LTP in the hippocampus:A mammalian model for learning

Hippocampus most studied because of it's organization--• complete circuitry represented in thin slices (100-400um thick)• can be placed in a dish for in vitro electrophysiological experiments• also thought to be important for memory consolidation in vivo

20 Copyright © 2004 Allyn and Bacon


typical LTP experiment1. stimulate neuron A, record PSP from neuron B2. stimulate neuron A tetanically (e.g. burst of stimuli @ 100 Hz)3. record PSP from B w/test pulses at varying intervals4. PSP augmented for several days or even up to months5. this augmentation is what is called LTP


CaMKII: Calcium/calmodulindependent kinase II

PKA, PKC: Protein kinase A, C

CREB: cAMP-responsive element-binding protein

Low-frequency stimulation results in small increases in [Ca2+] in the postsynaptic cell, which in turn results in fewer AMPA channels opening in response to glutamate. This is called low-frequency depression and is a mechanism for weakening synaptic strength.

http://www.sumanasinc.com/webcontent/anisamples/neurobiology/receptors.html



Organizational Aspects ofLearning and Memory

Three gross stages of learning and memory

AcquisitionStorageRetrieval


There are also qualitatively different kindsof learning

Declarativeepisodicsemantic

Procedural or non-declarativeskill learningprimingconditioning


Memory can be categorized according to its duration or persistence

Sensory tracese.g. iconic (visual) and echoic (auditory)

at most a few seconds in duration



Sensory tracesShort-term memory (STM) or working memory

information held in “consciousness”phonological loop (sub-vocal rehearsal)visual imageryepisodic buffer

can be initiated by current event or by recall from LTM controlled by “central executive”



Sensory tracesShort-term memory (STM) or working

memoryIntermediate-term memory

distinguishable from STM and LTM?up to a few days in duration




memoryIntermediate term memoryLong-term memory

indefinite duration, up to days


Memory can be characterized by its underlying physical bases

Sensory tracespersistent activity in sensory pathways




memoryreverberating circuitselectrical basislimited capacitycan be disrupted by intrusion of other activitydisplays both primacy and recency effects




memoryIntermediate term memory

biochemical basis?accessible by working memoryeventually irretrievable (storage or retrieval

failure?)





structural or anatomical basisprotein synthesis essentialunlimited(?) capacity





The case of Henry Molaison (H.M.)

H.M. suffered from epilepsy, with epileptic foci in both temporal lobes. It did not respond to drugs available at the time and was life-threatening.

Therefore, it was decided to remove the tissue in which the epileptiform activity originated.

H.M.’s surgery removed the amygdala, the hippocampus, and some of temporal lobe cortex.

Patient H.M.

EC: Entorhinal cortexH: HippocampusCer: CerebellumPH: Parahippocampal

cortex

Following surgery, H.M.’s memory of events prior to the surgery was intact (no retrograde amnesia).

But, he did display anterograde amnesia, the inability to form declarative memories after the surgery.

H.M.’s memory deficit was confined to verbal tasks, with motor learning (non-declarative memory) unaffected.

However, H.M. DID display anterograde amnesia for spatial tasks, e.g. navigating new environments

There Are Several Kinds of Memory and Learning

Studies in animals and other humans with brain damage showed that the H.M.s deficits were unlikely due solely to hippocampal damage. Other temporal lobe structures and the thalamus form a larger functional circuit necessary for consolidation of declarative memories.

Damage to other areas can also cause memory loss.

Patient N.A. has amnesia due to accidental damage to the dorsomedial thalamus, which is part of the same memory circuit affected by H.M.’s surgery.

Like Henry Molaison, he has short-term memory but cannot form declarative long-term memories.

Patient N.A.

damage of the dorsomedial thalamusdamage to floor of third ventricle, mammillary bodies

Korsakoff’s syndrome is a memory deficiency caused by lack of thiamine (vitamin B6)–often seen in chronic alcoholism.

Brain damage occurs in mammillary bodies and basal frontal lobes, which produces anterograde amnesia.

Patients often confabulate–fill in a gap in memory with a false memory that they fully believe to be true.

Korsakoff’s Syndrome


Three gross stages of learning and memory

AcquisitionStorageRetrieval

STM is susceptible to disruption prior to consolidation

•electroconvulsive shock (or ECT in clinical settings)can disrupt long-term memory by pulling those memoriesback into working memory at the time of ECT, which prevents re-consolidation

•head trauma generally results in retrograde amnesia, whose magnitude is inversely related to the age of the memory, by disturbing ongoing electrical activity

•traumatic events may also induce amnesia similar to head trauma or ECSe.g. placing rats in ice water immediately after training trial results in forgetting, or

amnesia

•may be a model for the loss of memory following psychological trauma (e.g. rape) in humans

LTM can be prevented by interfering with protein synthesis

Protein synthesis inhibitors block LTP and formation of memories in behavioral tasks.

The role of protein synthesis in response to environmental stimulation is very evident in the phenomenon of environmental enrichment

“Enrichment” studies are really studies of varying degrees of impoverishment. Rats living outdoors in natural envronmental enclosures exceed “enriched” rats on all measures

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Learning and Memory. Learning relatively permanent change in behavior as a function of training, practice or experience excludes behavioral changes resulting