Yuan-Yang Lai1,2,3, Tohru Kodama1,4, Kung-Chiao Hsieh2,5, Darian Nguyen1, Jerome M Siegel1,2. 1. Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA. 2. VA Greater Los Angeles HealthCare System, North Hills, CA. 3. Greater Los Angeles Veterans Research and Education Foundation, Los Angeles, CA. 4. Physiological Psychology Lab, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 5. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
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. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2020.
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. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2020.
Entities:
Keywords:
bicuculline; infusion; microdialysis; muscimol; restless legs syndrome
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