• Raghunandan Kumar Yadav, Mudasir Ahmad Khanday, and Birendra Nath Mallick.
• School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
• Behav. Brain Res. 2019 Dec 30; 376: 112169.

AbstractSubstantia nigra (SN) is rich in dopamine (DA)-ergic and GABA-ergic neurons, which project to and receive inputs from locus coeruleus (LC) and pedunculo-pontine tegmentum (PPT) possessing REM-OFF and REM-ON neurons, respectively. Loss of DA-ergic neurons and disturbed REM sleep (REMS) are associated with Parkinson's disease, depression and REMS behavior disorder. GABA-ergic projections from SN act pre-synaptically on the noradrenaline (NA)-ergic terminals coming from the LC-REM-OFF neurons onto the REM-ON neurons in PPT and play a critical role in initiating REMS. However, it was unknown how SN neurons get activated and whether the SN-DA-ergic neurons interact with the SN-GABA-ergic neurons for REMS regulation. In freely moving chronically prepared rats, neurons in SN (bilateral) were stimulated by local microinjection of Glutamate (Glut), sparing the fibers of passage, in the presence and absence of i.p. Haloperidol (Hal, DA-antagonist). In other sets, either Hal or Bicuculine (Bic, GABA-antagonist) alone or simultaneously was microinjected bilaterally into the SN and the effects on sleep-wakefulness were recorded. We observed that Glut in SN significantly increased REMS, which was prevented by Hal. REMS was decreased and increased by Hal and Bic, respectively; while their co-injection neutralized (ineffective) the individual effects. Combining these findings with previous reports suggest that the SN-DA-ergic neurons act on the SN-GABA-ergic to regulate REMS. The results advance our understanding of the neuro-anatomo-chemical connections and pharmaco-physiological regulation of REMS in health and diseases.Copyright © 2019 Elsevier B.V. All rights reserved.

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