Learning and Memory: Basic Mechanisms 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 behavior We refer to these changes as memories Experiences are not “stored”, rather they change the way we perform, perceive, think, and plan by physically changing the structure of the nervous system We 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” Example of pairing a puff of air in the eye of rabbit (to produce an eye blink response) with a tone If the weak synapse T (for tone) is activated at same time of strong synapse P (air puff), synapse T will become stronger and pair with the previously unconditioned motor response

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 neurons Induction 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

Neurons in entorhinal cortex relay incoming info to the granule cells of the dentate gyrus through a bundle of axons known as the perforant path. These neurons then project into field CA3 The terminals of the fibers from the dentate gyrus form synapses with dendritic spines of the pyramidal cells of field CA3 The axons of CA3 pyramidal cells send one branch to field CA1, the other to structures in the forebrain CA1 pyramidal cells provide the primary output of the hippocampus

Stimulation of LTP Stimulating electrode placed among axons in perforant path, and recording electrode placed in dentate gyrus, near granule cells. A single pulse is delivered to perforant path, and resulting population EPSP (an evoked potential that represents the EPSPs of a population of neurons) is recorded in the dentate gyrus. LTP can be induced by stimulating the axons in the perforant path with a burst of approx. 100 pulse within a few seconds If the response in the dentate gyrus is greater than it was before the burst, then LTP has occurred LTP can be produced in other parts of the hippocampal region and in other parts of the brain LTP in hippocampal slices can follow Hebb’s rule (associative LTP)

Role of NMDA receptors LTP requires two events: Activation of synapses Depolarization (due to quick, successive EPSPs) of the postsynaptic neuron NDMA 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 established Transmission 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 depolarized Involves a decrease in the number of AMPA receptors

Perceptual learning Learning provides us with the ability to perform an appropriate behavior in an appropriate situation The first part of learning involves learning to perceive particular stimuli Perceptual 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 cortex Visual learning can take place very rapidly Ventral 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 stimuli Learning 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 removed STM – memory for a stimulus that has just been perceived STM involves the activation of the new circuits formed during recognition Many 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 them The 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 receptors Extinction – 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 Functions 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