Embed Size (px)
DESCRIPTION
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 - PowerPoint PPT Presentation
Citation preview
Prof. Stephan Anagnostaras
Lecture 5: Memory Consolidation
Neurobiology of Learning and Memory
Multiple memory trace theory
McGaugh, 2000
Duncan, 1949
Squire: retention of TV shows after ECS
At least 2 kinds of consolidation
• Moleculartimescale of minutes to hours
• Systems timescale of weeks to years
Protein synthesis inhibition
Pavlovian fear conditioning protocol
• Bright White Lighting• Grumbling Noise• Ammonia Odor• Flat Shock Grids
Training Context
Shock US
Tone CS
Context CS
TRAINING
Pavlovian fear conditioning protocol
• Bright White Lighting• Grumbling Noise• Ammonia Odor• Flat Shock Grids
Testing Context
Context CS
TRAINING CONTEXT TEST
CR = Freezing
Freezing response assessed by blind time-sampling
Pavlovian fear conditioning protocol
• Baseline Period• Dark Red Lighting• Triangular Insert• White Noise• Vinegar Odor• Staggered Shock Grids
Alternate Context
TRAINING CONTEXT TEST
Tone CS
TONE TEST
CR = Freezing
Bourtchuladze et al., 1998
Anisomycin(protein synthesis)
Protein kinase Ainhibitor
Transgenic mice With reduced PKA
Josselyn et al., 2002 - CREB inhibition
CREB inducible repressor Anisomycin
Systems Consolidation
Amnesic humans display a time-limited retrograde amnesia of declarative memory
Temporally-graded retrograde amnesia
From Squire, Haist, & Shimamura (1989)
Zola-Morgan & Squire, 1991
Stuart Zola
Consolidation models
Rabbit (rat & mouse) Trace eyeblink depends on the hippocampus (Kim et al., 1995)
Within-subjects design (Anagnostaras et al., 1999)
REMOTE TRAINING
10 Tone-Shock Pairings
Within-subjects design
50 days later
REMOTE TRAINING
RECENT TRAINING
10 Tone-Shock Pairings(different tone)
Which contexts and tonesUsed were counterbalanced
Within-subjects design
50 days later next day
REMOTE TRAINING
RECENT TRAINING
LesionSHAMDH0–2–3–6AP
Electrolytic Dorsal Hippocampus Lesion
Within-subjects design
50 days later next day
10 dayrecovery
next day
REMOTE TRAINING
RECENT TRAINING
Sham or Hippocampus
Lesion
RECENT CONTEXT
REMOTECONTEXT
Test OrderCounterbalanced
DH lesions spare remote context memory
Remote Contextual Fear
DH lesions disrupt recent context memory
B12345678Minutes0255075100Remote Contextual Fear Recent Contextual Fear
DH lesions produce a time-limited retrograde amnesia of contextual fear
B12345678Minutes0255075100 C0RecentRemote(first six min)255075100Remote Contextual Fear Recent Contextual Fear Context Summary
Within-subjects design
50 days later next day
10 dayrecovery
next day
REMOTE TRAINING
RECENT TRAINING
Sham or Hippocampus
Lesion
RECENT CONTEXT
REMOTECONTEXT
Within-subjects design
50 days later next day
10 dayrecovery
next day
next day
next day
REMOTE TRAINING
RECENT TRAINING
Sham or Hippocampus
Lesion
RECENT CONTEXT
REMOTECONTEXT
REMOTE TONE
RECENT TONE
• Baseline Period• Dark Red Lighting• Quiet• Pine Shavings Odor• No Grids• Like Home Cage
Third Context for Tone Testing Only
Within-subjects design
50 days later next day
10 dayrecovery
next day
next day
next day
REMOTE TRAINING
RECENT TRAINING
Sham or Hippocampus
Lesion
RECENT CONTEXT
REMOTECONTEXT
REMOTE TONE
RECENT TONE
DH lesions spare remote tone fear memory
Remote Tone Fear
DH lesions spare recent tone fear memory
B0255075100MinutesBLBL134562Remote Tone Fear Recent Tone Fear
DH lesions spare tone fear memory
B0255075100MinutesBLBL134562Remote Tone Fear Recent Tone Fear
Remote(six min)C0255075100RecentTone Summary
DH lesions produce a highly selective deficit in recent contextual fear memory
DHSham
Context Summary0RecentRemote(first six min)255075100 Tone SummaryRemote(six min)0255075100Recent
Content could be:• Context-shock association• Just memory of the context
Systems gradientsin monkeys, rats,rabbits, and mice
Bontempi et al., 1999
Bontempi et al., 1999
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.
Semantic amnesia Hodges et al.focal temporal cortex damage
Frankland et al., 2001, NatureCortical disruption of CamKIIa: fear conditioning
Frankland et al., 2001, NatureCortical disruption of CamKIIa: water maze
Frankland et al., 2001, Nature
Cortical disruption of CamKIIa: water maze
hpc
cortex
Squire & Alvarez, 1995
McClelland,McNaughton,& O’Reilly, 1995
