VTA dopaminergic neurons regulate ethologically relevant sleep-wake behaviors.
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.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
Ada
A
Eban-Rothschild
Department of Physiology and Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, California, USA.
Gideon
G
Rothschild
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
William J
WJ
Giardino
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
Jeff R
JR
Jones
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
Luis
L
de Lecea
D000679:Amygdala / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology*; D008297:Male; D051379:Mice; D009425:Nesting Behavior / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*