Molecular Basis of Long-Term Memory Flashcards
What is the issue with phosphorylation of AMPA in LTP in regards to long-term memory consolidation?
Phosphorylation is not permanent and memory will be “erased” eventually. Proteins turnover and get degraded. We need a more permanent fix.
How to stabilize enhanced transmission?
Morphological changes at synapse lead to longterm changes in synaptic strength. Need new proteins via transcription (signal to nucleus).
Another fix for the transient effects of phosphorylation
Persistently active protein kinases maintain phosphorylation by AUTOPHOSPHORYLATION (no need for the activation by a second messenger). Leads to persistent phosphorylation even after Ca2+ levels drop.
What has the ability to autophosphorylate?
CaMKII
How long does autophosphorylation maintain an active form for?
Minutes to hours
What is required for longer-term (days/weeks) memory consolidation?
Protein synthesis
Anisomysin
A protein synthesis inhibitor that inhibits long-term memory consolidation
How is a new protein formed?
DNA –transcription–> mRNA –translation–> protein
Gene expression is regulated by
transcription factors
What did Kandel do with anisomysin?
Context conditioning: 1. expose mouse to context. 2. play sound. 3. play sound and shock -> mouse freezes 4. expose mouse to context -> mouse freezes for specific duration.
Still does this 24 hours later.
Anisomycin: 5. Inject mice with anisomycin. 6. Mice still have short term memory but not long term memory -> doesn’t freeze for as long on the following day.
Two transcription factors that are important in the consolidation of long-term memory
CREB-1 and CREB-2
CREB-1
Activator of gene expression
CREB-2
repressor of gene expression
How do CREB-1 and CREB-2 affect gene transcription?
When CREB-2 is bound to specific regions of a gene, no transcription occurs.
CREB-1 and CREB-2 are competitive; CREB-1 knocks out CREB-2 and binds to gene region.
CREB-1 is phosphorylated and transcription occurs.
What is the pathway that leads to the phosphorylation of CREB-1 and transcription?
NT release -> AMPA -> Na+ -> depolarization -> NMDA -> Ca2+ ->CaMK11, adenyl cyclase ->cAMP -> PKA -> phosphorylates CREB-1
Consolidation of long-term memories depends on
The relative activities of CREB-1 and CREB-2. Enhanced CREB-1 facilitates the consolidation of long-term memories.
Key requirement for LTM (days/weeks)
Synthesis of new proteins
Key requirement for short-term memory (minutes/hours)
Autophosphorylation
Requirement for induction of LTP?
Ca2+ influx
Shorter term LTP (minutes/hours) depends on
AMPA insertion
AMPA phosphorylation
CaMKII autophosphorylation
Longer term LTP depends on
Protein synthesis
Transcription factors
