Learning and Memory

1. Mind and Brain Learning and Memory Chapter 13

2. You are responsible for Chapter 13 (text and notes) for you final as well as all other chapters (and notes) covered in class.

3. http://www.youtube.com/watch?v=JliczINA__Y&feature=related

4. Chapter Overview • The Nature of Learning • Synaptic Plasticity: Long-Term Potentiation and Long-Term Depression • Perceptual Learning • Classical Conditioning • Instrumental Conditioning • Relational Learning

5. The Nature of Learning • Introduction • Learning refers to the process by which experiences change our nervous system and hence our behavior; we refer to these changes as memories • Experiences are not stored – they change the way we perceive, perform, think, and plan • They do so by physically changing the structure of the nervous system, altering neural circuits that participate in perceiving, performing, thinking and planning.

6. The Nature of Learning • Learning can take at least 4 basic forms • Perceptual Learning • Stimulus-Response Learning • Classical Conditioning • Instrumental Conditioning • Motor Learning • Relational Learning

7. The Nature of Learning • Perceptual Learning • Learning to recognize a particular stimulus • Primary function: ability to identify and categorize objects and situations • Each sensory system is capable of perceptual learning • Accomplished by changes in the sensory association cortex

8. The Nature of Learning • Stimulus-Response Learning • Learning to automatically make a particular response in the presence of a particular stimulus • Involves the establishment of connections between circuits involved in perception and those involved in movement • Classical conditioning • Instrumental conditioning

9. The Nature of Learning • Classical Conditioning • Unconditional Stimulus (US) – stimulus that produces a defensive or appetitive response. • Unconditional Response (UR) – response to the US. • Conditional Stimulus (CS) – stimulus, which when paired with the US during training, comes to elicit a learned response. • Conditional Response (CR) – response to the presentation of the CS.

10. Figure 13.1 A Simple Neural Model of Classical Conditioning

11. The Nature of Learning • Hebb Rule • hypothesis proposed by Donald Hebb that the cellular basis of learning involves strengthening of a synapse that is repeatedly active when the postsynaptic neuron fires.

12. Figure 13.1 A Simple Neural Model of Classical Conditioning

13. The Nature of Learning • Instrumental Conditioning (Operant conditioning) • learning procedure whereby the effects of a particular behavior in a particular situation increase (reinforce) or decrease (punish) the probability of the behavior. • Reinforcing Stimulus – appetitive stimulus that follows a particular behavior and thus makes the behavior become more frequent. • Punishing Stimulus – aversive stimulus that follows a particular behavior and thus makes the behavior become less frequent. • CC involves automatic or species-typical responses, but OC involves behaviors that have to be learned • CC involves an association between 2 stimuli, OC involves an association between a response and a stimulus. • OC is considered more flexible because it permits an organism to adjust its behavior according to the consequences of that behavior.

14. Figure 13.2 A Simple Neural Model of Instrumental Conditioning

15. The Nature of Learning • Motor Learning • Learning to make a new response • Component of stimulus-response learning

16. Figure 13.3 An Overview of Perceptual, Stimulus-Response (S-R), and Motor Learning.

17. The Nature of Learning • Relational Learning • More complex form of learning • Involves learning the relationships among individual stimuli • Includes the ability to recognize objects through more than one sensory modality • Involves learning the relative location of objects in the environment – spatial learning • Remembering the sequence in which events occurred during particular episodes – episodic learning • Hippocampus

18. Chapter Overview • The Nature of Learning • Synaptic Plasticity: Long-Term Potentiation and Long-Term Depression • Electrical stimulation of circuits within the hippocampus can lead to long-term synaptic changes that seem to be responsible for learning • Perceptual Learning • Classical Conditioning • Instrumental Conditioning • Relational Learning

19. See Figure 13.4 • Primary input to the HF comes from the EC • Axons of EC neurons pass through the perforant path and synapse with granule cells in the DG • From these cells, the mossy fibers project to the pyramidal cells in CA3 • From CA3, Schaffer collaterals project to CA1 cells • The 3 synapses know as the trisynaptic loop

20. Induction of LTP • A stimulating electrode is placed in the PP and a recording electrode is placed in the DG • A single pulse of electrical stimulation is delivered to the PP and the resulting population EPSP is recorded in the DG • Population EPSP is the evoked potential that represents EPSPs of a population of neurons. • LTP can be induced by stimulating the PP axons with a burst of electrical pulses (i.e., 100) within a few seconds

21. The size of the first population EPSP tells us the strength of the synaptic connections before LTP is induced Evidence that LTP has occurred is obtained by periodically delivering a single pulse and then measuring the response in the DG to see if it is bigger than the original response LTP

22. Synaptic Plasticity: LTP and LTD • LTP • Can be induced in other parts of the HF and in other brain regions • Can last for several months • Can be induced in slices and in living animals • Can follow the Hebb Rule (in slices) • Associative Long-Term Potentiation – long-term potentiation in which concurrent stimulation of weak and strong synapses to a given neuron strengthens the weak ones.

23. Figure 13.6 Associative Long-Term Potentiation

24. Figure 13.7 The Role of Summation in Long-Term Potentiation • Nonassociative LTP requires an additive effect • Series of pulses delivered at high rate will produce LTP • Same # of pulses given at slow rate will not (LTD) • Rapid rate of stimulation causes EPSPs to summate • Rapid stimulation depolarizes the postsynaptic membrane more than slow stimulation

25. Figure 13.8 Long-Term Potentiation • Experiments have shown that synaptic strengthening occurs when NTS binds with postsynaptic receptors located in a dendrite that is already depolarized • LTP requires 2 events • Activation of synapses • Depolarization of the postsynaptic membrane

26. Synaptic Plasticity: LTP and LTD • Role of NMDA Receptors • NMDA Receptor – specialized ionotropic glutamate receptor that controls a calcium channel that is normally blocked by Mg2+ ions. • Calcium ions enter the cells through channels controlled by NMDA receptors only when glutamate is present and the postsynaptic membrane is depolarized

27. Figure 13.9 The NMDA Receptor

28. Synaptic Plasticity: LTP and LTD • Role of NMDA Receptors • AP5 – 2-amino-5-phosphonopentanoate, a drug that blocks NMDA receptors. • Blocks the establishment of LTP

29. Synaptic Plasticity: LTP and LTD • Need glutamate & depolarization….but how do dendrites become depolarized if only axons can produce action potential? • Dendritic Spike – action potential that occurs in the dendrite of some types of pyramidal cells. • Threshold for activation is very high • Only occurs when action potential is triggered in the axon • Backwash of depolarization across cell body triggers dendritic spike • Whenever the axon of a pyramidal cell fires, all of its dendritic spines become depolarized for a brief time.

30. Synaptic Plasticity: LTP and LTD Simultaneous occurrence of synaptic activation and a dendritic spike strengthens the active synapse. • Magee and Johnston (1997) injected individual CA1 pyramidal cells in hippocampal slices with a fluorescent dye that permitted them to see the influx of calcium • When individual synapses became active at the same time that a dendritic spike had been triggered, Ca “hot spots” occurred near the activated synapses • Size of EPSPs produced by these activated synapses became larger – synapse became strengthened • TTX (blocks Na current) injected near dendrite – prevented dendritic spikes, no LTP!

31. Synaptic Plasticity: LTP and LTD • Role of NMDA receptors in Associative LTP • If weak synapses are active by themselves, nothing happens (NMDA receptors don’t open) • However, if the activity of strong synapses located elsewhere on the postsynaptic cell has caused the cell to fire, then a dendritic spike will depolarize the postsynaptic membrane enough to eject Mg ions from the Ca channels (of NMDA receptor) • If some synapses then become active, Ca will enter the dendritic spines and cause the synapses to become strengthened

32. Synaptic Plasticity: LTP and LTD • What is responsible for the increase in synaptic strength that occurs during LTP? • Dendrites on CA1 neurons contain 2 types of glutamate receptors: NMDA and AMPA

33. Synaptic Plasticity: LTP and LTD • Mechanisms of Synaptic Plasticity • AMPA Receptors – ionotropic glutamate receptor that controls a sodium channel; when open it produces EPSPs. • Strengthening of individual synapses is accomplished by the insertion of more AMPA receptors into the postsynaptic membrane of the dendritic spine • CaM-KII – type of calcium-calmodulin kinase, an enzyme that must be activated by calcium; may play a role in the establishment of LTP. • Nitric Oxide Synthase – enzyme responsible for the production of nitric oxide. • Drugs that block this enzyme prevent the establishment of LTP in CA1

34. Figure 13.16 Chemistry of LTP • Activation of terminal button releases glutamate, which binds with NMDA receptors in the postsynaptic membrane of the dendritic spine • If the membrane was depolarized by a dendritic spike, then calcium ions enter and activate CAM-KII • CAM-KII travels to the postsynaptic density and causes the insertion of AMPA receptors • LTP also initiates changes in synaptic structure and production of new synapses

35. Figure 13.16 Chemistry of LTP • The entry of calcium also activates NO synthase • This produces NO which diffuses out of the dendritic spine and back to the terminal button • The NO may then trigger chemical reactions that increase the release of glutamate • Long-lasting LTP also requires the synthesis of new proteins and the presence of dopamine

36. Synaptic Plasticity: LTP and LTD • Low-frequency stimulation of the synaptic inputs to a cell can decrease their strength • Long-Term Depression (LTD) also plays a role in learning…some synapses are strengthened and others weakened • 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. • Like LTP, requires activation of NMDA receptors • LTD involves a decrease in AMPA receptors

37. Synaptic Plasticity: LTP and LTD • Other Forms of LTP • Some forms of LTP do not involve NMDA receptors and are not blocked by AP5 (CA3). • For example, mossy fiber input from dentate gyrus to CA3 • Presynaptic changes only – no alterations in structure of dendritic spines

38. Chapter Overview • The Nature of Learning • Synaptic Plasticity: Long-Term Potentiation and Long-Term Depression • Perceptual Learning • Classical Conditioning • Instrumental Conditioning • Relational Learning

39. Figure 13.18 The Major Divisions of the Visual Cortex of the Rhesus Monkey • Primary visual cortex receives information from the lateral geniculate nucleus of the thalamus • Ventral Stream – pathway of information from the primary visual cortex to the temporal lobe, which is involved in object recognition (‘what’ pathway). • Dorsal Stream – pathway of information from the primary visual cortex to the parietal lobe, which is involved with perception of the location of objects (‘where’ pathway).

40. Chapter Overview • The Nature of Learning • Synaptic Plasticity: Long-Term Potentiation and Long-Term Depression • Perceptual Learning • Classical Conditioning • Instrumental Conditioning • Relational Learning

41. Figure 13.21 Conditioned Emotional Responses Information about the CS & US converge in the LA so synaptic changes responsible for learning could take place in this area Hebb rule - weak synapses (from tone) are strengthened when US activates neurons in the LA….LA neurons fire and activate CN …which evokes the response (Ch 11)

42. Classical Conditioning • Evidence for the involvement of lateral nucleus of the amygdala in CER • Changes in the LA responsible for CER learning involve LTP…and is accomplished through activation of the NMDA receptor • LTP • Injection of drugs that block LTP into the amygdala prevents the establishment of conditioned emotional responses • CER training (tone-shock pairings) causes AMPA receptors to be driven into dendritic spines of synapses between LA neurons and axons that provide auditory input

43. Classical Conditioning Rumpel et al., (2005) used a virus to insert a gene for a fluorescent dye coupled to a subunit of the AMPA receptor into the LA of rats…learning caused AMPA insertion They also inserted a gene for a dye coupled to a defective subunit of the AMPA receptor…the defective subunit prevented AMPA insertion and conditioning did not take place

44. Classical Conditioning • Infusion of many drugs into the LA that prevent LTP disrupt acquisition of a CER • Conclusion: • LTP in the amygdala, mediated by NMDA receptors, plays a critical role in the establishment of CER

45. Chapter Overview • The Nature of Learning • Synaptic Plasticity: Long-Term Potentiation and Long-Term Depression • Perceptual Learning • Classical Conditioning • Instrumental Conditioning • Relational Learning

46. Instrumental Conditioning • Instrumental conditioning involves a connection between a particular stimulus and a particular response • 2 major pathways between sensory association cortex and motor association cortex • Direct transcortical connections • Involved in episodic memory (along with HIP) • Connections via the basal ganglia and thalamus • 2 pathways play different roles

47. Basal Ganglia • Learned behaviors become automatic and routine, they are transferred to the basal ganglia • Leaving the transcortical circuits free to learn new tasks

48. Figure 13.23 The Basal Ganglia and Their Connections • Neostriatum (caudate nucleus & putamen) receives sensory input from all regions of the cerebral cortex. Also receives information from frontal lobes about movement (planned or in progress). • Outputs are sent to GP which sends information back to frontal cortex to premotor cortex (where plans for movement are made) and motor cortex (where movement is executed)

49. Instrumental Conditioning • Basal Ganglia • Studies of laboratory animals have indicated that: • lesions of the basal ganglia disrupt instrumental conditioning without affecting other forms of learning. • Fernadez-Ruiz et al., (2001) destroyed portions of the caudate and putamen that receive visual information from the ventral stream • Lesions did not disrupt visual perceptual learning • Impaired the monkeys’ ability to learn to make a visually guided operant response • Williams and Eskandar (2006): as monkeys learned a operant response, the rate of firing of single neurons in the caudate nucleus increased • The activity of caudate neurons is correlated with rate of learning • Blocking NMDA receptors in the basal ganglia with an injection of AP5 disrupts learning guided by a simple visual cue

50. Instrumental Conditioning - Reinforcement • Neural circuits involved in reinforcement discovered by Olds & Milner, 1954. • Reinforcement • Neural Circuits Involved in Reinforcement • Ventral Tegmental Area (VTA) – group of dopaminergic neurons in the ventral midbrain whose axons form the mesolimbic and mesocortical systems and are important in reinforcement. • Nucleus Accumbens – nucleus of the basal forebrain near the septum; receives dopamine from neurons of the VTA and is thought to be involved in reinforcement and attention. • See Figure 13.24