Chapter 13

Learning and Memory:Basic Mechanisms

The nature of learning

Learning refers to the processes by which experiences change our nervous system and hence our behaviorWe refer to these changes as memoriesExperiences are not “stored”, rather they change the way we perform, perceive, think, and plan by physically changing the structure of the nervous systemWe must be able to learn in order to adapt our behaviors to our changing environment

The nature of learning

4 basic forms of learning: Perceptual learning – ability to learn to recognize stimuli

that have been perceived before; enables us to identify and categorize objects; primarily accomplished by changes in the sensory association cortex

Stimulus-response learning – ability to learn to perform a particular behavior when a particular stimulus is present; involves establishment of connections between circuits involved in perception and those involved in movement

Two types: classical conditioning – when a stimulus that initially produces no

particular response (e.g. bell) is followed several times by an unconditioned stimulus (e.g. shock) that produces a defensive or appetitive response (the unconditioned response), the first stimulus (now called conditioned stimulus) itself evokes the response (now the conditioned response)

Operant conditioning (see slide 5)

The nature of learning

How does classical conditioning work in the brain?Hebb rule – the cellular basis of learning involves strengthening of a synapse that is repeatedly active when the postsynaptic neuron fires“Cells that fire together, wire together”

The nature of learning

Whereas classical conditioning involves an association between two stimuli, operant conditioning involves an association between a response and a stimulus

It permits an organism to adjust its behavior according to the consequences of that behavior

Reinforcing stimulus – an appetitive stimulus (e.g. food, water) that follows a particular behavior (e.g. lever press) and thus makes the behavior become more frequent

Punishing stimulus – an aversive stimulus (e.g. shock) that follows a particular behavior (e.g. lever press) and thus makes the behavior become less frequent

The nature of learning

Motor learning A component of S-R learning Learning to make a new response The more novel the behavior, the more the neural circuits

in the nervous system must be modified

Learning types summary

Learning and synaptic plasticity

Synaptic plasticity – changes in the structure or biochemistry of synapses that alter their effects on postsynaptic neuronsInduction of long-term potentiation (LTP)

Electrical stimulation of circuits within the hippocampal formation (forebrain structure of the temporal lobe, part of the limbic system) can lead to long-term synaptic changes that seem to be among those responsible for learning

LTP – a long-term increase in the excitability of a neuron to a particular synaptic input caused by repeated high-frequency activity of that input

Stimulation of LTP

Role of NMDA receptors

LTP requires two events: Activation of synapses Depolarization (due to quick, successive EPSPs) of the

postsynaptic neuronNDMA glutamate receptor plays a special role in this

Receptor found in the hippocampal formation, esp. in field CA1

Controls Ca2+ channel, and opens only when glutamate is present and when the postsynaptic membrane is depolarized (I.e. both NT and voltage-dependent ion channel)

AP5 – drug that blocks NMDA receptors; prevents establishment of LTP in field CA1 and the dentate gyrus; does not effect LTP that has already been establishedTransmission in potentiated synapses involves AMPA receptors (control Na+ channel)Dendritic spikes – an action potential that occurs in the dendrite of some types of pyramidal cells

Mechanisms of synaptic plasticity

What is responsible for the increases in synaptic strength that occur during LTP?

Individual synapses are strengthened (AMPA receptors) New synapses are produced

When LTP is induced, new AMPA receptors are inserted into the postsynaptic membrane

With more AMPA receptors present, the release of glutamate causes more postsynaptic potential

Entry of Ca2+ ions into dendritic spines is the event that begins the process that leads to LTP

The next step involves CaM-KII (type II calcium-calmodulin kinase), which is activated by calcium

Mechanisms of synaptic plasticity

LTP is accompanied by the growth of new synaptic connections

The dendritic spine will develop a projection that projects into the terminal button, dividing the active zone into 2 parts

LTP may also involve presynaptic changes (e.g increase in amount of glutamate released)

How? Nitric oxide (NO) may serve as a retrograde messenger with LTP

Long-term depression

A long-term decrease in the excitability of a neuron to a particular synaptic input caused by stimulation of the terminal button while the postsynaptic membrane is hyperpolarized or only slightly depolarizedInvolves a decrease in the number of AMPA receptors

Perceptual learning

Learning provides us with the ability to perform an appropriate behavior in an appropriate situationThe first part of learning involves learning to perceive particular stimuliPerceptual learning involves learning about things, not what to do when they are present

Involves learning to recognize new stimuli or to recognize changes in familiar stimuli

Appears to take place in appropriate regions of sensory association cortex

Learning to recognize particular stimuli

Objects are recognized visually by circuits of neurons in the visual association cortexVisual learning can take place very rapidlyVentral stream of visual assc. cortex – object recognition (“what”)Dorsal stream – perception of the location of objects (“where”)Damage to part of the ventral stream (in inferior temporal cortex) disrupts the ability to discriminate b/t different visual stimuliLearning to recognize a particular visual stimulus is accomplished by changes in synaptic connections in the inferior temporal cortex that establish new neural circuits

Perceptual short-term memory

Sometimes we are required to make a response to a stimulus, even after it has been removedSTM – memory for a stimulus that has just been perceivedSTM involves the activation of the new circuits formed during recognitionMany studies of STM involve a delayed matching-to-sample task (a task that requires the subject to indicate which stimulus has just been perceived)

Neurons in the inferior temporal cortex are activated at the sight of the stimulus and during the delay interval before choosing the correct stimulus

Perceptual STM involve other regions of the brain including the prefrontal cortex

Damage to this area results in failure to perform correctly on delayed MTS tasks using visual, tactile or auditory stimuli

Perceptual short-term memory

The activity in the visual assc. cortex and that in the prefrontal cortex appear to play different roles

Prefrontal cortex can hold info about visual stimulus, leaving the visual assc. cortex free

Prefrontal cortex can also represent newly perceived info in terms of previously learned associations (matching pairs of stimuli)

Classical conditioning

Most stimuli that cause an aversive emotional response are not intrinsically aversive, we have to learn to fear themThe central nucleus of the amygdala aids in forming SR learning (classical conditioning)

Info about the CS (e.g. tone) reaches the lateral nucleus of the amygdala, along with info about the US (e.g. shock)

The lateral nucleus sends projections to the central nucleus, which then evokes an unlearned emotional response

Changes in the lateral amygdala responsible for acquisition of a conditioned emotional response involve LTP, and is mediated by NMDA receptorsExtinction – the reduction or elimination of a CR by repeatedly presenting the CS without the US; also mediated by NMDA receptors

Instrumental conditioning and motor learning

Instrumental conditioning is the means by which we profit from experience

If response is already known, then we need strengthening of connections b/t neural circuits that detect relevant stimuli and those that control the relative response

If new response needed, the motor learning will take place

Basal ganglia Circuits responsible for instrumental conditioning begin in

sensory assc. cortex and end in motor assc. Cortex Two major pathways:

Direct transcortical connections – involved in STM, acquisition of episodic memories and of complex behaviors that involve deliberation or instruction

Connections via the basal ganglia and thalamus – involved once behaviors become automatic and routine

Instrumental conditioning and motor learning

Basal ganglia (con’t) Neostriatum (caudate and putamen) receive sensory info

from all regions of cortex; outputs sent to globus pallidus which projects to premotor and supplementary motor cortex

Damage to the caudate and putamen disrupts the ability to learn instrumental tasks

Individuals with Parkinson’s disease may not just have simple “motor deficits”; there may be an impairment in automated memories that control simply movements (e.g catching ourselves if we fall over)

Show impairment on a visual discrimination task

Premotor cortex Most output from basal ganglia is directed to premotor

cortex and supplementary motor area (involved in planning and execution of movements)

Instrumental conditioning and motor learning

Premotor cortex (con’t) Damage to supp. motor area disrupts ability to learn

sequences of responses in which the performance of one response serves as a signal that the next response must be made (e.g push in lever, then turn in to the left)

Premotor cortex plays a role in programming complex movements, and using sensory info to select a particular movement

Concerned with where in space a movement must be made, instead of which muscle contractions to make

Also involved in using arbitrary stimuli (e.g name for an object) to indicate what movement should be made (e.g. point to object)

Reinforcement

Neural circuits An animal’s behavior can be reinforced by electrical

stimulation of the brain The best and most reliable location for brain stimulation is

the medial forebrain bundle The activity of DA neurons plays an important role in

reinforcement: Mesolimbic system – begins in VTA and projects to amygdala,

hippocampus, and nucleus accumbens This pathway is important for reinforcing effects of brain

stimulation Natural reinforcers (e.g. food, sex, etc.) stimulates DA release

in the NA

Functions Detect presence of reinforcing stimulus Strengthen the connections b/t the neurons that detect the

discriminative stimulus (e.g. sight of lever) and the neurons that produce the instrumental response (e.g. press lever)

Reinforcement

Detecting reinforcing stimuli Reinforcement occurs when neural circuits detect a

reinforcing stimulus and cause the activation of DA neurons in VTA

If a stimulus causes an animal to engage in appetitive behavior (e.g approach stimulus vs. run away), then that stimulus can reinforce the animal’s behavior

Activated by unexpected reinforcing stimuli (i.e. something must be learned)

DA neurons in VTA activated by CR Amygdala, lateral hypothalamus and prefrontal cortex

important in detecting presence of reinforcing stimuli

Strengthening neural connections: DA and neural plasticity

DA enhances LTP Blocking NMDA receptors disrupts learning of new tasks for

reinforcement