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Prof. Stephan Anagnostaras Lecture 5: Memory Consolidation

Neurobiology of Learning and Memory. Prof. Stephan Anagnostaras Lecture 5: Memory Consolidation. Multiple memory trace theory. McGaugh, 2000. Duncan, 1949. Squire: retention of TV shows after ECS. At least 2 kinds of consolidation. Molecular timescale of minutes to hours Systems

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Prof. Stephan Anagnostaras Lecture 5: Memory Consolidation

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  1. Neurobiology of Learning and Memory Prof. Stephan Anagnostaras Lecture 5: Memory Consolidation

  2. Multiple memory trace theory McGaugh, 2000

  3. Duncan, 1949

  4. Squire: retention of TV shows after ECS

  5. At least 2 kinds of consolidation • Molecular timescale of minutes to hours • Systems timescale of weeks to years

  6. Protein synthesis inhibition

  7. Pavlovian fear conditioning protocol TRAINING Training Context • Bright White Lighting • Grumbling Noise • Ammonia Odor • Flat Shock Grids

  8. Pavlovian fear conditioning protocol TRAINING CONTEXT TEST Freezing response assessed by blind time-sampling CR = Freezing Testing Context • Bright White Lighting • Grumbling Noise • Ammonia Odor • Flat Shock Grids

  9. Pavlovian fear conditioning protocol TRAINING CONTEXT TEST TONE TEST CR = Freezing Alternate Context • Baseline Period • Dark Red Lighting • Triangular Insert • White Noise • Vinegar Odor • Staggered Shock Grids

  10. Bourtchuladze et al., 1998 Anisomycin (protein synthesis) Protein kinase A inhibitor Transgenic mice With reduced PKA

  11. Josselyn et al., 2002 - CREB inhibition CREB inducible repressor Anisomycin

  12. Systems Consolidation

  13. Temporally-graded retrograde amnesia Amnesic humans display a time-limited retrograde amnesia of declarative memory From Squire, Haist, & Shimamura (1989)

  14. Zola-Morgan & Squire, 1991 Stuart Zola

  15. Consolidation models

  16. Rabbit (rat & mouse) Trace eyeblink depends on the hippocampus (Kim et al., 1995)

  17. Within-subjects design (Anagnostaras et al., 1999) REMOTE TRAINING 10 Tone-Shock Pairings

  18. Within-subjects design REMOTE TRAINING RECENT TRAINING 10 Tone-Shock Pairings (different tone) Which contexts and tones Used were counterbalanced

  19. Within-subjects design REMOTE TRAINING RECENT TRAINING Lesion Electrolytic Dorsal Hippocampus Lesion

  20. Within-subjects design REMOTE TRAINING RECENT TRAINING Sham or Hippocampus Lesion REMOTE CONTEXT RECENT CONTEXT Test Order Counterbalanced

  21. DH lesions spare remote context memory Remote Contextual Fear

  22. DH lesions disrupt recent context memory Remote Contextual Fear Recent Contextual Fear

  23. DH lesions produce a time-limited retrograde amnesia of contextual fear Remote Contextual Fear Recent Contextual Fear Context Summary

  24. Within-subjects design REMOTE TRAINING RECENT TRAINING Sham or Hippocampus Lesion REMOTE CONTEXT RECENT CONTEXT

  25. Within-subjects design Third Context for Tone Testing Only REMOTE TRAINING RECENT TRAINING • Baseline Period • Dark Red Lighting • Quiet • Pine Shavings Odor • No Grids • Like Home Cage Sham or Hippocampus Lesion REMOTE CONTEXT RECENT TONE REMOTE TONE RECENT CONTEXT

  26. Within-subjects design REMOTE TRAINING RECENT TRAINING Sham or Hippocampus Lesion REMOTE CONTEXT RECENT TONE REMOTE TONE RECENT CONTEXT

  27. DH lesions spare remote tone fear memory Remote Tone Fear

  28. DH lesions spare recent tone fear memory Remote Tone Fear Recent Tone Fear

  29. DH lesions spare tone fear memory Remote Tone Fear Recent Tone Fear Tone Summary

  30. DH lesions produce a highly selective deficit in recent contextual fear memory Content could be: • Context-shock association • Just memory of the context

  31. Systems gradients in monkeys, rats, rabbits, and mice

  32. Bontempi et al., 1999

  33. Bontempi et al., 1999

  34. Bontempi et al., 1999 Figure 4 Factor analysis showing clustering of response accuracy and metabolic activity in mouse brain regions during retention testing. a, Retrieval performance of recent information (5 days retention) appears in the hippocampal cluster. b, Retrieval performance of remote memories (25 days retention) now appears in the cortical cluster. c, Correlation matrix table. Correlation coefficients for the 5- and 25-day retention groups are presented above and below the solid black line, respectively. Shaded boxes show significant correlations (P < 0.05). HPC, hippocampus; EC-SUB, entorhinal cortex/subiculum; aCC and pCC, anterior and posterior cingulate cortices; FC ant. and FC post., anterior and posterior parts of the frontal cortex; ACC nuc., accumbens nucleus.

  35. Semantic amnesia Hodges et al.focal temporal cortex damage

  36. Frankland et al., 2001, Nature Cortical disruption of CamKIIa: fear conditioning

  37. Frankland et al., 2001, Nature Cortical disruption of CamKIIa: water maze

  38. Frankland et al., 2001, Nature Cortical disruption of CamKIIa: water maze hpc cortex

  39. Squire & Alvarez, 1995

  40. McClelland, McNaughton, & O’Reilly, 1995

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