title: Perifornical orexinergic neurons modulate REM sleep by influencing locus coeruleus neurons in rats.
abstract: Activation of the orexin (OX)-ergic neurons in the perifornical (PeF) area has been reported to induce waking and reduce rapid eye movement sleep (REMS). The activities of OX-ergic neurons are maximum during active waking and they progressively reduce during non-REMS (NREMS) and REMS. Apparently, the locus coeruleus (LC) neurons also behave in a comparable manner as that of the OX-ergic neurons particularly in relation to waking and REMS. Further, as PeF OX-ergic neurons send dense projections to LC, we argued that the former could drive the LC neurons to modulate waking and REMS. Studies in freely moving normally behaving animals where simultaneously neuro-chemo-anatomo-physio-behavioral information could be deciphered would significantly strengthen our understanding on the regulation of REMS. Therefore, in this study in freely behaving chronically prepared rats we stimulated the PeF neurons without or with simultaneous blocking of specific subtypes of OX-ergic receptors in the LC while electrophysiological recording characterizing sleep-waking was continued. Single dose of glutamate stimulation as well as sustained mild electrical stimulation of PeF (both bilateral) significantly increased waking and reduced REMS as compared to baseline. Simultaneous application of OX-receptor1 (OX1R) antagonist bilaterally into the LC prevented PeF stimulation-induced REMS suppression. Also, the effect of electrical stimulation of the PeF was long lasting as compared to that of the glutamate stimulation. Further, sustained electrical stimulation significantly decreased both REMS duration as well as REMS frequency, while glutamate stimulation decreased REMS duration only.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: R C
authors.initials: RC
authors.lastname: Choudhary
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: M A
authors.initials: MA
authors.lastname: Khanday
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: A
authors.initials: A
authors.lastname: Mitra
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: remsbnm@yahoo.com.
authors.forename: B N
authors.initials: BN
authors.lastname: Mallick
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography; D018698:Glutamic Acid / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000378:metabolism; D000068797:Orexins; D010671:Phenylurea Compounds / Q000494:pharmacology; D017208:Rats, Wistar; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D002491:Central Nervous System Agents; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D010671:Phenylurea Compounds; C542397:SB 408124; D018698:Glutamic Acid
keywords: SB-418024; chemical stimulation; electrical stimulation; glutamate; orexin 1 receptor