Table of Contents
Long-term Depression and Depotentiation
LTP - LTD Opposites?
Functional Roles for LTP-LTD
Cerebellar Function
Cerebellum mediated learning
E.g. Conditioned Eyeblink
LTD occurs via the same “learning” pathway
Specificity of LTD
Role of CF activation in LTD
Role of PF input in LTD
LTD inducion - postsyn. mechanisms
Model of NO in Cerebellar LTD
PF LTD Expression
Local Calcium Release in Dendritic Spines Required for Long-Term Synaptic Depression
Evaluating steps of the LTD Induction Model using Mouse and Rat Mutants
Experimental Procedures
Electron Microscopy of Cerebellar Dendritic Spines
Similarly for the (dl) mouse SER is missing from spines
Immunocytochemistry for the IP3 receptor
IP3 Receptors absent from Mutant Dendritic Spines
Anatomical Summary
No Cerebellar LTD in Rat dop mutant
No cerebellar LTD in mouse dl mutant
Normal Synapses in rat mutants
PF Synaptic transmission normal
Rat dop Parallel Fiber mediated Paired Pulse Facilitation - unchanged
Climbing Fiber synaptic properties normal - AMPAr mediated currents
Climbing Fiber PPD somewhat greater in the rat dop mutant
Voltage gated calcium currents are normal
Dendritic Calcium signals normal in more mature control and mutant mice Purkinje cells
LTD induction mechanisms intact in the Mouse Mutant
Localization of mGluR receptors
EM immunocytochemistry localizes the mGluR to spine heads in both controls and rat mutants
Influx versus release of Ca2+ from stores
PKC found in both the Control and Mutant Rat Purkinje Cells Molecular Layer and CBs
LTD induction mechanisms intact in the Mouse Mutant
Caged IP3 exps in Cerebellar PC
Uncaging IP3 in dendrites increases calcium in the mutant spines, but with a longer latency in most spines
Calcium released during IP3 uncaging diffuses from dendrite to spines
Uncaging calcium directly into spines rescues LTD in the mutants
Model for IP3 signaling during LTD at PF-PC synapses
Summary Spines, IP3 and LTD at cerebellar synapses
Hippocampal Synaptic Plasticity - Theoretical Framework
BCM theory (Bienenstock, Cooper, and Munro, 1982)
Dependence of Rat hippocampal CA1 LTD / LTP on frequency of stimulation
LTD - dependence on exact amount of postsynaptic calcium through the NMDAr
Synaptic learning rule ~BCM theory
Induction of LTP or LTD
LTD
Expression of LTD/LTP
LTD removes AMPAr even to the point of creating “silent” synapses
Evidence for AMPAr internalization
mGluR - LTD is not mediated through same mechanisms as NMDAR - LTD
Depotentiation
Pathways to Time-sensitive Depotentiation
Unlike hippocampal synapses Cerebellar LTD is not reversible by LTP
Unlike hippocampal synapses Cerebellar LTP is not reversible by LTD
Summary LTD Common Themes
NMDA synaptic responses discovered during postsynaptic depolarization
Morphological Correlates of LTP - Spine swelling, Neck widening
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