A common hub for sleep and motor control in the substantia nigra

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Science  24 Jan 2020:
Vol. 367, Issue 6476, pp. 440-445
DOI: 10.1126/science.aaz0956

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Interneurons control brain arousal states

The underlying circuit mechanisms coordinating brain arousal and motor activity are poorly understood. Liu et al. found that glutamic acid decarboxylase 2 (GAD2)–expressing, but not parvalbumin-expressing, interneurons in a part of the brain known as the substantia nigra promote sleep (see the Perspective by Wisden and Franks). Parvalbuminergic neurons fire at higher rates in states of high motor activity, and their activation increases movement termination consistent with the function of the substantia nigra in suppressing unwanted movements during action selection. By contrast, GAD2 neurons are preferentially active in states of low motor activity. In addition to motor suppression, their activation powerfully enhances the transition from quiet wakefulness to sleep, which differ mainly in the arousal level rather than motor behavior. GAD2 interneurons thus provide general suppression of both motor activity and brain arousal to promote states of quiescence.

Science, this issue p. 440; see also p. 366


The arousal state of the brain covaries with the motor state of the animal. How these state changes are coordinated remains unclear. We discovered that sleep–wake brain states and motor behaviors are coregulated by shared neurons in the substantia nigra pars reticulata (SNr). Analysis of mouse home-cage behavior identified four states with different levels of brain arousal and motor activity: locomotion, nonlocomotor movement, quiet wakefulness, and sleep; transitions occurred not randomly but primarily between neighboring states. The glutamic acid decarboxylase 2 but not the parvalbumin subset of SNr γ-aminobutyric acid (GABA)–releasing (GABAergic) neurons was preferentially active in states of low motor activity and arousal. Their activation or inactivation biased the direction of natural behavioral transitions and promoted or suppressed sleep, respectively. These GABAergic neurons integrate wide-ranging inputs and innervate multiple arousal-promoting and motor-control circuits through extensive collateral projections.

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