title: GABA-mediated control of hypocretin- but not melanin-concentrating hormone-immunoreactive neurones during sleep in rats.
abstract: The perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the regulation of behavioural arousal. The PF-LHA contains several cell types including neurones expressing the peptides, hypocretin (HCRT; also called orexin) and melanin-concentrating hormone (MCH). Evidence suggests that most of the PF-LHA neurones, including HCRT neurones, are active during waking and quiescent during non-rapid eye movement (non-NREM) sleep. The PF-LHA contains local GABAergic interneurones and also receives GABAergic inputs from sleep-promoting regions in the preoptic area of the hypothalamus. We hypothesized that increased GABA-mediated inhibition within PF-LHA contributes to the suppression of neuronal activity during non-REM sleep. EEG and EMG activity of rats were monitored for 2 h during microdialytic delivery of artificial cerebrospinal fluid (aCSF) or bicuculline, a GABAA receptor antagonist, into the PF-LHA in spontaneously sleeping rats during the lights-on period. At the end of aCSF or bicuculline perfusion, rats were killed and c-Fos immunoreactivity (Fos-IR) in HCRT, MCH and other PF-LHA neurones was quantified. In response to bicuculline perfusion into the PF-LHA, rats exhibited a dose-dependent decrease in non-REM and REM sleep time and an increase in time awake. The number of HCRT, MCH and non-HCRT/non-MCH neurones exhibiting Fos-IR adjacent to the microdialysis probe also increased dose-dependently in response to bicuculline. However, significantly fewer MCH neurones exhibited Fos-IR in response to bicuculline as compared to HCRT and other PF-LHA neurones. These results support the hypothesis that PF-LHA neurones, including HCRT neurones, are subject to increased endogenous GABAergic inhibition during sleep. In contrast, MCH neurones appear to be subject to weaker GABAergic control during sleep.
authors.affiliation: Research Service (151A3), Veteran Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA. noor@ucla.edu
authors.forename: Md Noor
authors.initials: MN
authors.lastname: Alam
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.forename: Tariq
authors.initials: T
authors.lastname: Bashir
authors.forename: Natalia
authors.initials: N
authors.lastname: Suntsova
authors.forename: Melvi M
authors.initials: MM
authors.lastname: Methippara
authors.forename: Ronald
authors.initials: R
authors.lastname: Szymusiak
authors.forename: Dennis
authors.initials: D
authors.lastname: McGinty
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D016762:Genes, fos / Q000502:physiology; D007026:Hypothalamic Area, Lateral / Q000502:physiology / Q000648:ultrastructure; D007028:Hypothalamic Hormones / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D008543:Melanins / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000502:physiology*; D000068797:Orexins; D010907:Pituitary Hormones / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012894:Sleep Stages / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D005680:gamma-Aminobutyric Acid; C019463:melanin-concentrating hormone; D001640:Bicuculline