A presynaptic role for PKA in synaptic tagging and memory

Alan Jung Park; Robbert Havekes; Jennifer HK Choi; Vincent Luczak; Ting Nie; Ted Huang; Ted Abel

doi:10.1016/j.nlm.2014.05.005

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A presynaptic role for PKA in synaptic tagging and memory

Journal article

Peer reviewed

A presynaptic role for PKA in synaptic tagging and memory

Alan Jung Park, Robbert Havekes, Jennifer HK Choi, Vincent Luczak, Ting Nie, Ted Huang and Ted Abel

Neurobiology of learning and memory, Vol.114, pp.101-112

10/2014

DOI: 10.1016/j.nlm.2014.05.005

PMCID: PMC4143446

PMID: 24882624

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Abstract

[Display omitted] •PKA anchoring regulates the size of the readily releasable synaptic vesicle pool.•Localized PKA regulates the level of synaptic vesicle protein 2 (SV2).•Synaptic tagging requires presynaptically compartmentalized PKA signaling.•Contextual fear memory formation requires presynaptically localized PKA signaling. 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.

Synaptic tagging

Ht31

PKA anchoring

SV2

PKA

Details

Title: Subtitle: A presynaptic role for PKA in synaptic tagging and memory
Creators: Alan Jung Park - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Robbert Havekes - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Jennifer HK Choi - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Vincent Luczak - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Ting Nie - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Ted Huang - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA
Resource Type: Journal article
Publication Details: Neurobiology of learning and memory, Vol.114, pp.101-112
DOI: 10.1016/j.nlm.2014.05.005
PMID: 24882624
PMCID: PMC4143446
NLM abbreviation: Neurobiol Learn Mem
ISSN: 1074-7427
eISSN: 1095-9564
Publisher: Elsevier Inc
Grant note: name: NWO, award: 825.07.029; name: HFSP, award: RGSP/2005
Language: English
Date published: 10/2014
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065736102771

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