Memory Consolidation PDF

H.M. Perceptual and motor skills are intact Ability to form new memories is disrupted Loss of declarative memory: episodic and semantic memory Memory intact up to 11 years prior to accident Then remembered less and less up to the accident (temporally graded retrograde amnesia) LTP...

H.M. Perceptual and motor skills are intact Ability to form new memories is disrupted Loss of declarative memory: episodic and semantic memory Memory intact up to 11 years prior to accident Then remembered less and less up to the accident (temporally graded retrograde amnesia) LTP – a brief review Glu activates AMPAR ! Na+ flows into the cell ! depolarizes the membrane ! NMDAR loses Mg2+ block ! NMDAR let in Ca2+ ! activates Calmodulin ! CaMKII ! actin breakdown ! spine enlargement ! AMPAR recruitment ! PKA ! CREB ! mRNA production ! production of proteins involved in synaptic plasticity Synaptic consolidation requires protein synthesis Protein synthesis inhibitors injected into the hippocampus prevent memory consolidation Protein synthesis inhibitors prevents HFS from producing long-lasting LTP (L-LTP) Amnesia due to MTL damage Amnesia: loss of memory and/or ability to learn Retrograde: loss of memory of more recent memory before trauma but able to remember memories more distant and form new memories Storage failure: permanent failure Retrieval failure: temporary amnesia Anterograde: inability to form new memories Consolidation deficit Where are older memories stored if not in the MTL? Hippocampal involvement in retrieval Contextual fear conditioning paradigm Lesion MTL and look if rats can retrieve the memory at different days Different results: Lesion at 28 days is relatively fully intact (Kim & Fanselow) Lesion at 100 days is relatively fully intact (Maren) Lesion at 50 days is relative fully intact (Anagnostaras) Standard Consolidation Model David Marr first proposed that hippocampus would rapidly learn memories and offload the memories to cortex through replay events Forward replay: activation of neurons in order Reverse replay: activation of neurons in reverse order The modern standard consolidation model suggests that both hippocampus and cortex begin storing a memory, but that hippocampal activity is necessary early in the memory stage to fully ‘activate’ the memory Hippocampus: strong connections initially ! weaker connections ! no longer stores the memory Can be reactivated Cortex: weak connections initially ! stronger connections (plasticity) ! cell assembly in the cortex Replay in hippocampus Replay even in place cell: reactivation of neurons in the same sequence during activity Offline replay: resting state/sleeping Online replay: while active Replay in hippocampus = start wave ripples can be seen through the same sequence of neuron activation is contracted – can be up to 20x the speed of the initial memory Memory reconsolidation Memory reconsolidation: Processes by which a LTM is recalled and then consolidated once again Can lead to the maintenance, strengthening and updating of LTM During recall, memory reactivation will strengthen the synaptic connections between neurons Strengthening the connections in the cortex over time Memory reactivation during consolidation can be due to either: replay cued recall of the memory Cue-dependent amnesia: evidence for memory reconsolidation Methods: CS: White noise, US: Shock ECS: Electroconvulsive shock Results: ECS disrupts a memory only if it has been reactivated (active/labile) introduced active trace theory to explain these results: a memory is put into an ‘active’ and labile state during reactivation Active trace theory Active trace theory: An ‘active’ memory is susceptible to disruption, but also allows for stronger consolidation Recall = strengthens the memory trace But transfer to hippocampus for consolidation places it at its most vulnerable state Memory reconsolidation in hippocampus Protein synthesis inhibitors injected into the hippocampus disrupts stable LTM Injection 1h before training: No disruption after 1h (short term) Great disruptions starting 2d later Injection 1h after training Disruption starting day 7 Injection 1 day after training Disruption starting day 8 Injection 2 days after training No disruption Memory recall transitions from the MTL to cortex Methods: Rats trained, recent memory test (5 days) and remote memory test (10 days) Results: Recent memory test: no activity in ACC, FC activity in hippocampus, basal ganglia Remote memory test:  activity in ACC, FC, PC, Low/no activity in drip New context test (creation of new memory) Activity in Hip CaMKII regulates LTP differently across brain regions Protein activated when Ca2+ enters the cell Starts the cellular changes needed for LTP Maybe different types of CaMKII expressed in Hippocampus vs Cortex: alpha-CaMKII: LTP is relatively the same in hippocampus = synaptic consolidation alpha-CaMKII: if removal of alpha-CaMKII = no synaptic consolidation in the cortex Cortex learns more slowly Multiple Trace Theory Episodic memory in MTL damaged patients was not vivid and appeared to be a completely disrupted (flat) retrograde effect: able to recall semantic memories of past events rather than clear autobiographical recall of the events Need MTL to recreate the episodic memories suggestion that hippocampus was required for the episodic experience of all memories Prefrontal cortical involvement in the standard model of consolidation Maybe PFC has inhibitory control over hippocampus and that would explain how the hippocampus loses the memory trace Neurogenesis in the hippocampus dentate gyrus Hippocampus is one of two locations in the brain where new neurons are created (neurogenesis) To make room for new neurons, old/unused neurons die