Research article summary (published 9 Jun 2008):

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

Full 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.

Author information

Author/s: Isiegas, Carolina (C); McDonough, Conor (C); Huang, Ted (T); Havekes, Robbert (R); Fabian, Sara (S); Wu, Long-Jun (LJ); Xu, Hui (H); Zhao, Ming-Gao (MG); Kim, Jae-Ick (JI); Lee, Yong-Seok (YS); Lee, Hye-Ryeon (HR); Ko, Hyoung-Gon (HG); Lee, Nuribalhae (N); Choi, Sun-Lim (SL); Lee, Jeong-Sik (JS); Son, Hyeon (H); Zhuo, Min (M); Kaang, Bong-Kiun (BK); Abel, Ted (T);

Affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. cisiegas(-atsign-)sas.upenn.edu

Grants: 5F31MH069136-02 (Agency:NIMH NIH HHS) ; T32MH014654 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2008-Jun; vol 28 (issue 24) : pp 6220-30

Dates: Created 2008/06/13; Completed 2008/07/10;

PMID: 18550764, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adrenergic alpha-Agonists - pharmacology Analysis of Variance Animals Behavior, Animal - drug effects Conditioning (Psychology) - drug effects; physiology Cyclic AMP - metabolism Cyclic AMP Response Element-Binding Protein - metabolism Electric Stimulation - methods Fear - drug effects Hippocampus - cytology; drug effects; metabolism Long-Term Potentiation - drug effects; physiology; radiation effects

Memory - drug effects; physiology Mice Mice, Inbred C57BL Mice, Transgenic Neurons - drug effects; physiology Octopamine - pharmacology Patch-Clamp Techniques - methods Pattern Recognition, Visual - drug effects; physiology Phosphopyruvate Hydratase - metabolism Receptors, Biogenic Amine - genetics Synaptic Transmission - drug effects; physiology; radiation effects

Associated Chemicals: Adrenergic alpha-Agonists (0) ; Cyclic AMP Response Element-Binding Protein (0) ; Receptors, Biogenic Amine (0) ; norsynephrine receptor (0) ; Octopamine (104-14-3) ; Cyclic AMP (60-92-4) ; Phosphopyruvate Hydratase (EC 4.2.1.11)

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