Journal article
Astrocyte-Derived Adenosine and A1 Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice
The Journal of neuroscience, Vol.31(19), pp.6956-6962
05/11/2011
DOI: 10.1523/JNEUROSCI.5761-10.2011
PMCID: PMC3140051
PMID: 21562257
Abstract
Sleep deprivation (SD) can have a negative impact on cognitive function, but the mechanism(s) by which SD modulates memory remains unclear. We have previously shown that astrocyte-derived adenosine is a candidate molecule involved in the cognitive deficits following a brief period of SD (
Halassa et al., 2009
). In this study, we examined whether genetic disruption of soluble
N
-ethylmaleimide-sensitive factor attached protein (SNARE)-dependent exocytosis in astrocytes (dnSNARE mice) or pharmacological blockade of A
1
receptor signaling using an adenosine A
1
receptor (A
1
R) antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), could prevent the negative effects of 6 h of SD on hippocampal late-phase long-term potentiation (L-LTP) and hippocampus-dependent spatial object recognition memory. We found that SD impaired L-LTP in wild-type mice but not in dnSNARE mice. Similarly, this deficit in L-LTP resulting from SD was prevented by a chronic infusion of CPT. Consistent with these results, we found that hippocampus-dependent memory deficits produced by SD were rescued in dnSNARE mice and CPT-treated mice. These data provide the first evidence that astrocytic ATP and adenosine A
1
R activity contribute to the effects of SD on hippocampal synaptic plasticity and hippocampus-dependent memory, and suggest a new therapeutic target to reverse the hippocampus-related cognitive deficits induced by sleep loss.
Details
- Title: Subtitle
- Astrocyte-Derived Adenosine and A1 Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice
- Creators
- Cédrick Florian - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104Christopher G Vecsey - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104Michael M Halassa - Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114Philip G Haydon - Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.31(19), pp.6956-6962
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5761-10.2011
- PMID
- 21562257
- PMCID
- PMC3140051
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 05/11/2011
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065837302771
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