Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 24, Pages 6220-6230Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2935-07.2008
Keywords
cAMP; conditional genetic system; octopamine; synaptic plasticity; memory; retrieval
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Funding
- NIMH NIH HHS [R01 MH060244-08, F31 MH069136, 5F31MH069136-02, T32 MH014654, R01 MH060244, T32MH014654] Funding Source: Medline
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Consistent evidence from pharmacological and genetic studies shows that cAMP is a critical modulator of synaptic plasticity and memory formation. However, the potential of the cAMP signaling pathway as a target for memory enhancement remains unclear because of contradictory findings from pharmacological and genetic approaches. To address these issues, we have developed a novel conditional genetic system in mice based on the heterologous expression of an Aplysia octopamine receptor, a G-protein-coupled receptor whose activation by its natural ligand octopamine leads to rapid and transient increases in cAMP. We find that activation of this receptor transgenically expressed in mouse forebrain neurons induces a rapid elevation of hippocampal cAMP levels, facilitates hippocampus synaptic plasticity, and enhances the consolidation and retrieval of fear memory. Our findings clearly demonstrate that acute increases in cAMP levels selectively in neurons facilitate synaptic plasticity and memory, and illustrate the potential of this heterologous system to study cAMP-mediated processes in mammalian systems.
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