Substantia nigra pars reticulata-mediated sleep and motor activity regulation

Sleep. 2021 Jan 21;44(1):zsaa151. doi: 10.1093/sleep/zsaa151.

Abstract

Study objectives: The substantia nigra pars reticulata (SNR) is a major output nucleus of the basal ganglia. Animal studies have shown that lesions of the SNR cause hyposomnia and motor hyperactivity, indicating that the SNR may play a role in the control of sleep and motor activity.

Methods: Eight 8- to 10-week-old adult male Sprague-Dawley rats were used. After 3 days of baseline polysomnographic recording, dialysates were collected from the lateral SNR across natural sleep-wake states. Muscimol and bicuculline were microinfused into the lateral SNR.

Results: We found that GABA release in the lateral SNR is negatively correlated with slow wave sleep (SWS; R = -0.266, p < 0.01, n = 240) and positively correlated with waking (R = 0.265, p < 0.01, n = 240) in rats. Microinfusion of muscimol into the lateral SNR decreased sleep time and sleep quality, as well as eliciting motor hyperactivity in wake and increased periodic leg movement in SWS, while bicuculline infused into the lateral SNR increased sleep and decreased motor activity in SWS in rats. Muscimol infusion skewed the distribution of inter-movement intervals, with most between 10 and 20 s, while a flat distribution of intervals between 10 and 90 s was seen in baseline conditions.

Conclusions: Activation of the lateral SNR is important for inducing sleep and inhibiting motor activity prior to and during sleep, and thus to the maintenance of sleep. Abnormal function of the lateral SNR may cause hyposomnia and motor hyperactivity in quiet wake and in sleep.

Keywords: bicuculline; infusion; microdialysis; muscimol; restless legs syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • GABA Antagonists
  • Male
  • Motor Activity
  • Pars Reticulata*
  • Rats
  • Rats, Sprague-Dawley
  • Sleep
  • Substantia Nigra*
  • gamma-Aminobutyric Acid

Substances

  • GABA Antagonists
  • gamma-Aminobutyric Acid