Journal article
Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss
The Journal of neuroscience, Vol.34(47), pp.15715-15721
11/19/2014
DOI: 10.1523/JNEUROSCI.2403-14.2014
PMCID: PMC4236401
PMID: 25411499
Abstract
The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.
Details
- Title: Subtitle
- Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss
- Creators
- Robbert Havekes - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, havekesr@sas.upenn.edu abele@sas.upenn.eduVibeke M Bruinenberg - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Center for Behavior and Neurosciences, University of Groningen, Groningen, The Netherlands, andJennifer C Tudor - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104Sarah L Ferri - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104Arnd Baumann - Forschungszentrum Jülich, Institute of Complex Systems, Zelluläre Biophysik (ICS-4), D-52425 Jülich, GermanyPeter Meerlo - Center for Behavior and Neurosciences, University of Groningen, Groningen, The Netherlands, andTed Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, havekesr@sas.upenn.edu abele@sas.upenn.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.34(47), pp.15715-15721
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.2403-14.2014
- PMID
- 25411499
- PMCID
- PMC4236401
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- 5K12GM081529 / NIGMS NIH HHS 1R01MH086415 / NIMH NIH HHS R01 MH086415 / NIMH NIH HHS T32 NS007413 / NINDS NIH HHS K12 GM081259 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/19/2014
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065735602771
Metrics
17 Record Views