Neurobiology of Learning and Memory Prof. Stephan Anagnostaras Lecture 5: Memory Consolidation Multiple memory trace theory Duncan, 1949 McGaugh, 2 Squire: retention of TV shows after ECS At least 2 kinds of consolidation Molecular timescale of minutes to hours Systems timescale of weeks to years 1
Protein synthesis inhibition Pavlovian fear conditioning protocol Training Context Shock US Bright White Lighting Grumbling Noise Ammonia Odor Flat Shock Grids Pavlovian fear conditioning protocol Pavlovian fear conditioning protocol TEST CR = Freezing Testing Context Freezing response assessed by blind time-sampling Bright White Lighting Grumbling Noise Ammonia Odor Flat Shock Grids TEST TEST Alternate Context CR = Freezing Baseline Period Dark Red Lighting Triangular Insert White Noise Vinegar Odor Staggered Shock Grids Bourtchuladze et al., 1998 Anisomycin (protein synthesis) Josselyn et al., 22 - CREB inhibition CREB inducible repressor Anisomycin Protein kinase A inhibitor Transgenic mice With reduced PKA 2
Temporally-graded retrograde amnesia Amnesic humans display a time-limited retrograde amnesia of declarative memory Systems Consolidation From Squire, Haist, & Shimamura (1989) Zola-Morgan & Squire, 1991 Consolidation models Stuart Zola Rabbit (rat & mouse) Trace eyeblink depends on the hippocampus (Kim et al., 1995) (Anagnostaras et al., 1999) 1 Tone-Shock Pairings 3
1 Tone-Shock Pairings (different tone) Which contexts and tones Used were counterbalanced Electrolytic Dorsal lesions spare remote context memory or Freezing (% time) 1 A Remote Contextual Fear 1 2 3 4 5 6 7 8 Minutes Test Order Counterbalanced lesions disrupt recent context memory lesions produce a time-limited retrograde amnesia of contextual fear A 1 Remote Contextual Fear Recent Contextual Fear A 1 Remote Contextual Fear Recent Contextual Fear Context Summary Freezing (% time) Freezing (% time) 1 2 3 4 5 6 7 8 Minutes 1 2 3 4 5 6 7 8 Minutes 4
or Third Context for Tone Testing Only Baseline Period Dark Red Lighting Quiet Pine Shavings Odor No Grids Like Home Cage or lesions spare remote tone fear memory or Remote Tone Fear lesions spare recent tone fear memory lesions spare tone fear memory Remote Tone Fear Recent Tone Fear Remote Tone Fear Recent Tone Fear Tone Summary 5
lesions produce a highly selective deficit in recent contextual fear memory Content could be: Context-shock association Systems gradients in monkeys, rats, rabbits, and mice Just memory of the context 1 Context Summary 1 Tone Summary Remote Recent (first six min) Remote Recent (six min) Bontempi et al., 1999 Bontempi et al., 1999 Semantic amnesia Hodges et al. focal temporal cortex damage 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 ( days retention) now appears in the cortical cluster. c, Correlation matrix table. Correlation coefficients for the 5- and -day retention groups are presented above and below the solid black line, respectively. Shaded boxes show significant correlations ( P <.5). 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. 6
Frankland et al., 21, Nature Frankland et al., 21, Nature Cortical disruption of CamKIIa: fear conditioning Frankland et al., 21, Nature Squire & Alvarez, 1995 Cortical disruption of CamKIIa: water maze Cortical disruption of CamKIIa: water maze hpc cortex McClelland, McNaughton, & O Reilly, 1995 7