Chapter 13

1. Chapter 13 Learning and Memory: Basic Mechanisms

2. 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

3. 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)

4. 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”

5. 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

7. 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

8. Learning types summary

9. 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

11. Stimulation of LTP

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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)

20. 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

21. 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

22. 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)

23. 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)

24. 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)

25. 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