A presynaptic role for PKA in synaptic tagging and memory.

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TitleA presynaptic role for PKA in synaptic tagging and memory.
Publication TypeJournal Article
Year of Publication2014
AuthorsPark, AJung, Havekes, R, Choi, JHk, Luczak, V, Nie, T, Huang, T, Abel, T
JournalNeurobiol Learn Mem
Volume114
Pagination101-112
Date Published2014 Oct
ISSN1095-9564
KeywordsA Kinase Anchor Proteins, Animals, Cyclic AMP-Dependent Protein Kinases, Fear, GTP-Binding Proteins, Hippocampus, Membrane Glycoproteins, Memory, Mice, Mice, Transgenic, Nerve Tissue Proteins, Neuronal Plasticity, Presynaptic Terminals, Proteins, Synapses, Synaptosomal-Associated Protein 25
Abstract

Protein kinase A (PKA) and other signaling molecules are spatially restricted within neurons by A-kinase anchoring proteins (AKAPs). Although studies on compartmentalized PKA signaling have focused on postsynaptic mechanisms, presynaptically anchored PKA may contribute to synaptic plasticity and memory because PKA also regulates presynaptic transmitter release. Here, we examine this issue using genetic and pharmacological application of Ht31, a PKA anchoring disrupting peptide. At the hippocampal Schaffer collateral CA3-CA1 synapse, Ht31 treatment elicits a rapid decay of synaptic responses to repetitive stimuli, indicating a fast depletion of the readily releasable pool of synaptic vesicles. The interaction between PKA and proteins involved in producing this pool of synaptic vesicles is supported by biochemical assays showing that synaptic vesicle protein 2 (SV2), Rim1, and SNAP25 are components of a complex that interacts with cAMP. Moreover, acute treatment with Ht31 reduces the levels of SV2. Finally, experiments with transgenic mouse lines, which express Ht31 in excitatory neurons at the Schaffer collateral CA3-CA1 synapse, highlight a requirement for presynaptically anchored PKA in pathway-specific synaptic tagging and long-term contextual fear memory. These results suggest that a presynaptically compartmentalized PKA is critical for synaptic plasticity and memory by regulating the readily releasable pool of synaptic vesicles.

DOI10.1016/j.nlm.2014.05.005
Alternate JournalNeurobiol Learn Mem
PubMed ID24882624
PubMed Central IDPMC4143446
Grant ListK12 GM081259 / GM / NIGMS NIH HHS / United States
R01 AA018060 / AA / NIAAA NIH HHS / United States
R01 AA 018060 / AA / NIAAA NIH HHS / United States
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