Table of Contents
Long-term Potentiation (LTP): Focus on Hippocampus NMDA-receptor dependent and NMDA-receptor independent LTP
Long Term Potentiation
Discovered in vivo in dentate gyrus
LTP demonstrated at Exp Pathway
LTP Induction in Hippocampal Slices
Early Post tetanic Effects
Post Synaptic Induction of LTP via NMDAr channels
Short term Postsynaptic effects
Short term Postsynaptic effects
Criteria for a signaling molecule to be directly involved in LTP induction
CaMKII - key postsynaptic component of LTP
CA3 -> CA1 LTP
Presynaptic Expression of Early LTP
Late phase LTP results in more peaks, suggesting new synapses brought on line
NMDA only “Silent Synapses”
NMDA synaptic responses discovered during postsynaptic depolarization
Conversion of Silent synapses to active Synapses via AMPAr insertion
Summary
Candidate Retrograde signals
Associativity of LTP
Associativity of LTP
Two different synapses to same cell can show different types of LTP
New Gene Expression with LTP
Immediate Early Genes, LTP and memory
Zif268
Immediate early Gene Zif268 KO
No change in Gross Anatomy in Zif268 KO
GABAergic intereneurons still present
Synapses are present
Paired Pulse Facilitation is Normal
PPF - normal in the Zif268 KO
Early Phase of LTP is normal
Late LTP is diminished in both +/- and -/-
Spatial learning Impairment
Spatial Memory Impairment
Extensive Training overcomes the Spatial Learning and Memory Deficits
Taste Aversion Memory Impairment (tested at 24 hours)
Impaired Discrimination Memory
Impaired Discrimination Memory Percent time spent with Novel Objects
Immediate Early Gene Zif268
Is there morphological evidence for altered synapses during LTP?
History
1949 Hebb’s Postulate
Structural changes that could mediate late LTP
Morphological Correlates of LTP Changes in Synapse Number
Question: Generation of New Synapses
Morphological Correlates of LTP - Spine swelling, Neck widening
Examples of changes in existing synapse structure that have been reported after LTP
Existing Synaptic Changes cont.
Most of the above studies
New synapses are continuously generated in the brain.
LTP in Hippocampal Slices
LTP Within Slices
Adult Hippocampal Slices
LTP does NOT produce new synapses or modify existing synapses in mature hippocampus
Instead new spines generated during periods of inactivity in mature hippocampus
Dendrite Tips
LTP in Immature Hippocampal Neurons
Hippocampal Dendritic Filopodia at PN6
Immature Dendrite
Role of activity in filopodial outgrowth
Role of synaptically released glutamate in dendritic spine formation
Glutamate application / spine formation
Subset of synapses change connectivity with LTP in organotypic slices
Transien increase in perforated PSDs
Blockade of LTP by KN93 prevents morphological correlates
Enduring increase in the frequency of multiple spine boutons where both spines arise from the same parent dendrite
Summary - morphology and LTP
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