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- Title
Astrocyte-Derived Adenosine and A<sub>1</sub> Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice.
- Authors
Florian, Cédrick; Vecsey, Christopher G.; Halassa, Michael M.; Haydon, Philip G.; Abel, Ted
- 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 A1receptor signaling using an adenosineA1receptor (A3R) antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), could prevent the negative effects of6hof SDonhippocampal 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 adenosineA3R 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.
- Subjects
SLEEP deprivation; PHYSIOLOGICAL stress; ASTROCYTES; ADENOSINES; NEUROPLASTICITY
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 19, p6956
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5761-10.2011