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

doi:10.1523/JNEUROSCI.2935-07.2008

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

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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, …

The Journal of neuroscience, Vol.28(24), pp.6220-6230

06/11/2008

DOI: 10.1523/JNEUROSCI.2935-07.2008

PMCID: PMC2909468

PMID: 18550764

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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.

Memory - drug effects

Synaptic Transmission - physiology

Receptors, Biogenic Amine - genetics

Fear - drug effects

Phosphopyruvate Hydratase - metabolism

Octopamine - pharmacology

Hippocampus - drug effects

Pattern Recognition, Visual - physiology

Patch-Clamp Techniques - methods

Long-Term Potentiation - drug effects

Neurons - physiology

Long-Term Potentiation - physiology

Behavior, Animal - drug effects

Synaptic Transmission - drug effects

Neurons - drug effects

Cyclic AMP - metabolism

Electric Stimulation - methods

Conditioning (Psychology) - drug effects

Conditioning (Psychology) - physiology

Mice, Inbred C57BL

Mice, Transgenic

Hippocampus - cytology

Long-Term Potentiation - radiation effects

Hippocampus - metabolism

Animals

Synaptic Transmission - radiation effects

Analysis of Variance

Cyclic AMP Response Element-Binding Protein - metabolism

Pattern Recognition, Visual - drug effects

Adrenergic alpha-Agonists - pharmacology

Mice

In Vitro Techniques

Memory - physiology

Details

Title: Subtitle: A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval
Creators: Carolina Isiegas - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. cisiegas@sas.upenn.edu
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
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.28(24), pp.6220-6230
Publisher: United States
DOI: 10.1523/JNEUROSCI.2935-07.2008
PMID: 18550764
PMCID: PMC2909468
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: T32MH014654 / NIMH NIH HHS T32 MH014654 / NIMH NIH HHS 5F31MH069136-02 / NIMH NIH HHS R01 MH060244 / NIMH NIH HHS R01 MH060244-08 / NIMH NIH HHS F31 MH069136 / NIMH NIH HHS
Language: English
Date published: 06/11/2008
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065736602771

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