Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 38, Pages 10278-10288Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1602-07.2007
Keywords
cAMP-dependent protein kinase; A kinase-anchoring proteins; hippocampus; spatial memory; synaptic plasticity; LTP
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Funding
- NIMH NIH HHS [R01 MH060244, R01 MH060244-07] Funding Source: Medline
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Studies of hippocampal long-term potentiation (LTP), a cellular model of memory storage, implicate cAMP-dependent protein kinase (PKA) in presynaptic and postsynaptic mechanisms of LTP. The anchoring of PKA to AKAPs (A kinase-anchoring proteins) creates compartmentalized pools of PKA, but the roles of presynaptically and postsynaptically anchored forms of PKA in late-phase LTP are unclear. In this study, we have created genetically modified mice that conditionally express Ht31, an inhibitor of PKA anchoring, to probe the roles of anchored PKA in hippocampal LTP and spatial memory. Our findings show that at hippocampal Schaffer collateral CA3-CA1 synapses, theta-burst LTP requires presynaptically anchored PKA. In addition, a pool of anchored PKA in hippocampal area CA3 is required for spatial memory. These findings reveal a novel and significant role for anchored PKA signaling in cellular mechanisms underlying memory storage.
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