Astrocyte-Derived Adenosine and A1 Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice
Author(s)
Florian, Cedrick; Vecsey, Christopher G.; Haydon, Philip G.; Abel, Ted; Halassa, Michael M.
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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 A1 receptor signaling using an adenosine A1 receptor (A1R) 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 A1R 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.
Date issued
2011-05Department
Massachusetts Institute of Technology. Department of Brain and Cognitive SciencesJournal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Florian, C. et al. “Astrocyte-Derived Adenosine and A1 Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice.” Journal of Neuroscience 31.19 (2011): 6956-6962. Web. 8 Feb. 2012.
Version: Final published version
ISSN
0270-6474
1529-2401