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Publication : A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval.

First Author  Isiegas C Year  2008
Journal  J Neurosci Volume  28
Issue  24 Pages  6220-30
PubMed ID  18550764 Mgi Jnum  J:137375
Mgi Id  MGI:3799405 Doi  10.1523/JNEUROSCI.2935-07.2008
Citation  Isiegas C, et al. (2008) A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval. J Neurosci 28(24):6220-30
abstractText  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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