Amnesia in Humans and Animals: Neurobiology of Memory

1. Neurobiology of Learning and Memory Prof. Stephan Anagnostaras Lecture 4: Amnesia in humans and animals

2. Memory structures

3. RB

4. Animal models of memory •HM inspired investigation of MTL animal models of memory •no verbal abilities in animals, so can’t use terms “explicit” or “declarative” memory •CAN look at what happens with hpc damage… (area affected in many human amnesics)

5. Object recognition memory task: Non-recurring items Delayed Non-Match-to-Sample (DNMS) •usually w/monkeys (but babies, too), can also do w/rats (Mumby box) •give sample object w/reward underneath •take away objects & wait delay period •present 2 objects (1 from before (sample)): need to pick NEW object (the non-match w/food under) •can increase delay b/w sample & pair to test memory more finely

6. DNMS task in monkeys

8. Effects of lesions on Delayed Non-Match-to-Sample (DNMS) •MTL-lesioned monkeys won’t pick new object (can’t remember sample object from before) Which part of MTL is important? •monkeys w/hpc lesions do poorly •rhinal ctx lesions have even BIGGER effect (problem w/ shorter delay) Which area is typically more affected in humans w/ brain damage? •Remember that hpc is particularly susceptible to damage from ischemia (stroke, heart attack)

9. Rhinal cortex overlays the hippocampus (hpc)

13. Summary of monkey studies • Hippocampus critical • Surrounding cortex exacerbates deficit • Amygdala not critical for these tasks

15. Memory in rats ( and mice): what is it that they must remember? Several views on hippocampus • Explicit memory is an example of the kind of memory the hippocampus processes • The hippocampus is only involved in explicit memory • The hippocampus is specialized for spatial memory and was co-opted for explicit memory when language developed

18. Several paradigms • Will talk about fear conditioning later • Spatial memory paradigms - Olton Radial arm maze - Morris Watermaze • Nonspatial paradigms - object recognition - spatial recognition - social recognition - social transmission - relational learning

19. Win-Shift spatial working memory on the Olton radial arm maze: Unshifted Spatial delayed non-matching to sample • –Food deprived mice are • searching for food pellets • –Isolated noise-buffered room • –Maze itself is isotropic • –Lots of distal extramaze cues 4 Random Arms Baited-Open 4 Arms Closed 5 Minute Maximum (Trial over when 4 correct) Errors = Revisits

20. Win-Shift spatial working memory on the Olton radial arm maze: Unshifted 4 Random Arms Baited-Open 4 Arms Closed 5 Minute Maximum (Trial over when 4 correct) Errors = Revisits

21. Win-Shift spatial working memory on the Olton radial arm maze: Shifted 4 Random Arms Baited-Open 4 Arms Closed 5 Minute Maximum (Trial over when 4 correct) Errors = Revisits 4 Shifted Arms Baited All Arms Open 5 Minute Maximum Errors = Revisits between or within phase

22. Win-Shift spatial working memory on the Olton radial arm maze: Shifted 4 Random Arms Baited-Open 4 Arms Closed 5 Minute Maximum (Trial over when 4 correct) Errors = Revisits 4 Shifted Arms Baited All Arms Open 5 Minute Maximum Errors = Revisits between or within phase

23. Win-Shift A phase: 4 random arms baited and open

24. Win-Shift B phase: opposite 4 baited; all open 1. Mouse placed in home cage 2. Maze cleaned with ethanol --Delay period-- 3. Mouse placed into enclosed center

25. Win-Shift B phase: opposite 4 baited; all open poor memory Ach receptor knock-out (subtype= M1)

26. Water Maze Hidden Platform Task •Use spatial cues in room (posters, etc) to locate submerged platform (same place ea. time) •Measure latency to mount plaform & swim path (distance traveled to platform)

27. Watermaze day 1

28. Watermaze day 3

29. Watermaze day 5

30. Hpc lesions disrupt hidden platform water maze learning (spatial learning) Hippocampal lesion Normal Neocortical Control lesion

31. Watermaze

33. Watermaze visible

37. Eichenbaum, 2000

38. Hippocampal (hpc) place cells: encode memory for spatial location? T-maze: Run to particular arm to receive reward Nature Reviews Neuroscience1; 41-50 (2000) Left-turn trials: individual hpc cells fired as rat passed through each of a series of locations (red circled areas and arrows) running up the stem of the T-maze and turning onto the left choice arm where it received a reward (black well). Right-turn trials: a diff set of cells fired as the animal passed through the same set of locations on the stem as well as when it turned onto the right choice arm (green circles and arrows). These findings indicate that the hpc represents each type of trial separately.

39. Social Transmission of Food Preferences Eichenbaum, 2000

40. Mumby Box (Clark, West, Zola, & Squire, 2001)

41. Object Recognition

42. Rampon et al. (2000) - CA1 NMDA KO

43. Social recognition

44. Social recognition Delay

45. Hippocampal Lesion Anisomycin CREB -/- Kogan, Frankland, & Silva, 2000

46. Social discrimination: non-match to sample 4 min baseline + 4 min test

47. Social discrimination: non-match to sample 4 min baseline + 4 min test 4 min baseline + 4 min test Delay

48. xSocial discrimination