PT - JOURNAL ARTICLE AU - Cédrick Florian AU - Christopher G. Vecsey AU - Michael M. Halassa AU - Philip G. Haydon AU - Ted Abel TI - Astrocyte-Derived Adenosine and A<sub>1</sub> Receptor Activity Contribute to Sleep Loss-Induced Deficits in Hippocampal Synaptic Plasticity and Memory in Mice AID - 10.1523/JNEUROSCI.5761-10.2011 DP - 2011 May 11 TA - The Journal of Neuroscience PG - 6956--6962 VI - 31 IP - 19 4099 - http://www.jneurosci.org/content/31/19/6956.short 4100 - http://www.jneurosci.org/content/31/19/6956.full SO - J. Neurosci.2011 May 11; 31 AB - 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.