1. Please go watch these 2 lectures after class 2008 HHMI lecture by Eric Kandel and Tom Jessell This week http://media.hhmi.org/hl/08Lect1.html More history about early works on mapping the brain function Next week http://media.hhmi.org/hl/08Lect4.html

2. Where is the seat of the soul? Socrates (469-399 BC) “… brain may be the originating power of the perceptions of hearing and sight and smell, and memory and opinion may come from them…” Aristotle (384-322 BC) cardiocentric view of mental function function of the brain is to cool the heart

3. Hermann Ebbinghaus The 1st psychologist study memory scientifically. Used introspection to study forgetting in himself list of 12-16 consonant-vowel-consonant nonsense syllabus (Ex:KEG, MIW). The study of learning is closely related to the beginning of experimental psychology (~1900) Origins of the study of learning and memory On Memory: An Investigation in Experimental Psychology in 1885.

4. Several modern disciplines study of learning and memory Psychology – classification of learning and memory Physiology/Anatomy – Which part of brain is important for learning and memory Molecular Biology – Molecular mechanism of learning and memory

6. Patient HM Most famous case reported by Scoville & Milner (1957) HM: bilateral medial temporal lobe lesion for status epilepticus in 1953

7. The medial temporal lobe and memory storage

8. Importance of hippocampus in long-term memory formation: case of H.M.

9. Amnesia: severe memory loss 1. Retrograde amnesia: cannot recall events that occurred prior to the brain trauma. 2. Anterograde amnesia: cannot recall events that occurs after the brain trauma. Amnesia: Partial or total loss of memory, usually resulting from shock, psychological disturbance, brain injury, or illness.

10. H.M. showed normal motor learning and long term memory

11. Subjects were presented with common words 1.asked to recall the words (free recall) 2.given the first three letters of a word (priming) H.M. perform well in priming

12. Evidence of postmorbid acquisition of semantic knowledge

13. H.M.‘s specific memory deficit IQ and personality unchanged Normal learning and short-term memory Normal long-term memory for facts before operation Loss of information acquired just before the operation Unable to transfer new short-term memory into new long-term memory (explicit memory) Normal procedural (motor) memory

14. What we learn from H.M.’s case We have two types of memory: Short term and long term. The hippocampus is not involved in the formation of short term memory and retrieval of long-term memories. The hippocampus is not involved in 'procedural memories‘. The hippocampus is not be involved in personality, IQ and other cognitive functions. The hippocampus is involved in transferring short term explicit memory to long term memory.

15. The anatomical organization of the hippocampus

16. pyramidal cell layer CA=Cornu Ammonis DG=dentate gyrus Sub=subiculum EC= Entorhinal Cortex Hippocampus anatomy sub hilus granular cell layer

17. The input and output pathways of the hippocampal formation

18. Right hippocampus - spatial memories

19. London Taxi Drivers : Structural MRI & Neuropsychological Analysis Bus drivers were not found such correlation

20. Memory Types of memory: – short-term (working) memory temporary limited capacity needs rehearsal – long-term memory 'permanent' greater capacity no continual rehearsal needed

21. CPU RAM Hard disk Current view of explicative memory

22. Short-term memory Works like RAM memory in computers; provides a working space. A limited capacity for 7±2 independent information. Last only few seconds to minutes Vulnerable to interruption or interference The information held in short-term memory may be: – recently processed sensory input – items recently retrieved from long-term memory

23. Ways to move information to long term memory 1. Senses and emotions 2. Repetition and Rehearsal 3. Organization Principles

24. Senses and emotions Where were you on the following day? September 01, 2004 September 11, 2001 September 21, 1999 0-9-3-5-1-5-7-3-7-6

25. 25 Repetition and Rehearsal Effortful learning usually requires rehearsal or conscious repetition. Ebbinghaus studied rehearsal by using nonsense syllables: TUV YOF GEK XOZ

26. Organization Principles Acronyms are another way of chunking information to remember it. HOMES = Huron, Ontario, Michigan, Erie, Superior abuse Ab = away, from

27. Long-term memory Long-term memory store containing the accumulated knowledge base Characteristics – Duration: Hours to years – Capacity: Huge - possibly limitless Hippocampal system would mediate the initial steps of long- term storage. It would then slowly transfer information into the neocortical storage system.

28. Forms of long-term memory Explicit Implicit

29. Memory can be classified as implicate or explicit on the basis of how information is stored and recalled

30. Explicit versus Implicit Memory Explicit (or declarative) memory – recalled by a deliberate, conscious effort. - semantic memory (facts) - episodic memory (events) Implicit memory ( nondeclarative) – a memory that is recalled unconsciously. Stored in perceptual, motor and emotional circuits. - procedural memory (swimming, biking) - associative learning (conditioning) - nonassociative learning - priming

31. Semantic vs. episodic memory Episodic Memory refers to memories for particular events that have been experienced. Semantic Memory refers to knowledge such as vocabularies, concepts, numbers or facts.

32. associative agnosia apperceptive agnosia damage to the posterior parietal cortexdamage to the occipital lobes Selective lesions in the posterior parietal cortex produce selective defects in semantic knowledge

33. Explicit knowledge involves four distinct processes Encoding: process of newly learned information. Consolidation: make new information more stable for long-term storage. Synthesis of new proteins is required. Storage: the mechanism and sites to retain memory over time. Retrieval: recall and use of the stored information. The more association, the stronger memory Retrieval of information is most effective when it occurs in the same cues.

35. Implicit memory Implicit memory ( nondeclarative) – a memory that is recalled unconsciously. Stored in perceptual, motor and emotional circuits. - procedural memory (swimming, biking) - associative learning (conditioning) - nonassociative learning - priming Builds up slowly, through repetition over many trials, and is expressed primarily in performance, not in words. Does not depend on conscious processes.

36. Learning of implicit memory Non-associative learning: learns about the properties of a single stimulus – Habituation – Sensitization Associative learning: learns about the relationship between two stimuli or between a stimulus and a behavior – Classical conditioning (Pavlovian conditioning) – Operant conditioning (Instrumental conditioning)

37. Nonassociative Learning Habituation : decrease in response to a repeated stimulus not accompanied by changes in other stimuli Sensitisation: an increase in response to a moderate stimuli as a result of a previous exposure to a strong stimulus 如入鮑魚之肆，久而不聞其臭 一朝被蛇咬，十年怕草繩

38. Associative Learning Classical conditioning Operant conditioning learning a relationship between two stimuli learning a relationship between a behavior and the consequences

39. US → UR CS+ US → UR CS → CR （ salivation ） (US) (CS) (UR) (CR) Classical conditioning

40. Classical Conditioning – Unconditioned stimulus (US): unrelated to the response that eventually will be learned. – Conditioned stimulus (CS): neutral response – During conditioning, the CS and US are paired over many trials – Test of learning: Does the CS alone produce a response? CS-US paired CR TRIALS UR

41. Pavlov believed that conditioning strengthened connections between the CS center and US center in the brain. Pavlov’s view of the physiology of learning

42. Contest vs. cued fear conditioning CS= something neutral (tone, light) US= aversive stimulus (loud noise, shock )

43. The formation of classical conditioned response depend on the correlation between CS and US

44. 10 Tone-Shock Pairings 10 Tone only 1 Tone-Shock Pairings Extinction Training Re-train Extinction and spontaneous recovery ExtinctionTrainingRe-train

45. Remote training 10 Tone-Shock Pairings Freezing Importance of hippocampus in contextual fear conditioning test

46. Remote Training Recent Training 10 light-Shock Pairings 50 days later Importance of hippocampus in contextual fear conditioning test

47. Lesion Electrolytic Dorsal Hippocampus Lesion With in 24 hr Importance of hippocampus in contextual fear conditioning test Remote Training Recent Training 50 days later

48. Sham or Hippocampus Lesion DH SHAM next day 10 day recovery C 0 Recent Remote (first six min) 25 50 75 100 % freezing Importance of hippocampus in contextual fear conditioning test Remote Training Recent Training 50 days later Remote Recent Next day

49. Operant Behavior Associative learning process between a stimulus and a response. The term operant comes from the verb to operate and refers to behavior that operates on the environment to produce a consequence. Not automatic Operant conditioning as a process, has evolved over species history and is based on genetic endowment.

50. Operant learning The mouse is “operating” on its environment by pressing the lever in the box and receiving a food reward. Voluntary and goal directed Controlled by its consequences Strengthened if rewarded or punished

51. Associative learning is not random but is constrained by the biology of the organism

52. Hebbian learning Donald Hebb (1949) - When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.