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

Carolina Isiegas, Conor McDonough, Ted Huang, Robbert Havekes, Sara Fabian, Long Jun Wu, Hui Xu, Ming Gao Zhao, Jae Ick Kim, Yong Seok Lee, Hye Ryeon Lee, Hyoung Gon Ko, Nuribalhae Lee, Sun Lim Choi, Jeong Sik Lee, Hyeon Son, Min Zhuo, Bong Kiun Kaang, Ted Abel

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6220-6230
Number of pages11
JournalJournal of Neuroscience
Volume28
Issue number24
DOIs
StatePublished - Jun 11 2008

Keywords

  • Conditional genetic system
  • Memory
  • Octopamine
  • Retrieval
  • Synaptic plasticity
  • cAMP

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Isiegas, C., McDonough, C., Huang, T., Havekes, R., Fabian, S., Wu, L. J., Xu, H., Zhao, M. G., Kim, J. I., Lee, Y. S., Lee, H. R., Ko, H. G., Lee, N., Choi, S. L., Lee, J. S., Son, H., Zhuo, M., Kaang, B. K., & Abel, T. (2008). A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval. Journal of Neuroscience, 28(24), 6220-6230. https://doi.org/10.1523/JNEUROSCI.2935-07.2008