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Publication : VTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors.

First Author  Eban-Rothschild A Year  2016
Journal  Nat Neurosci Volume  19
Issue  10 Pages  1356-66
PubMed ID  27595385 Mgi Jnum  J:238226
Mgi Id  MGI:5818626 Doi  10.1038/nn.4377
Citation  Eban-Rothschild A, et al. (2016) VTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors. Nat Neurosci 19(10):1356-66
abstractText  Dopaminergic ventral tegmental area (VTA) neurons are critically involved in a variety of behaviors that rely on heightened arousal, but whether they directly and causally control the generation and maintenance of wakefulness is unknown. We recorded calcium activity using fiber photometry in freely behaving mice and found arousal-state-dependent alterations in VTA dopaminergic neurons. We used chemogenetic and optogenetic manipulations together with polysomnographic recordings to demonstrate that VTA dopaminergic neurons are necessary for arousal and that their inhibition suppresses wakefulness, even in the face of ethologically relevant salient stimuli. Nevertheless, before inducing sleep, inhibition of VTA dopaminergic neurons promoted goal-directed and sleep-related nesting behavior. Optogenetic stimulation, in contrast, initiated and maintained wakefulness and suppressed sleep and sleep-related nesting behavior. We further found that different projections of VTA dopaminergic neurons differentially modulate arousal. Collectively, our findings uncover a fundamental role for VTA dopaminergic circuitry in the maintenance of the awake state and ethologically relevant sleep-related behaviors.
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