GABAergic regulation of the perifornical-lateral hypothalamic neurons during non-rapid eye movement sleep in rats.
The perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the regulation of behavioral arousal. The PF-LHA predominantly contains neurons that are active during behavioral and cortical activation and quiescent during non-rapid eye movement (nonREM) sleep, that is, are nonREM-off neurons. Some in vitro and in vivo studies indicate that PF-LHA neurons, including hypocretin-expressing neurons, are under GABAergic control. However, a role of GABA in suppressing the discharge of PF-LHA neurons during spontaneous nonREM sleep has not been confirmed. We recorded the sleep-wake discharge profiles of PF-LHA neurons and simultaneously assessed the contributions of local GABA(A) receptor activation and blockade on their wake- and nonREM sleep-related discharge activities by delivering GABA(A) receptor agonist, muscimol (500 nm, 5 microM, and 10 microM) and its antagonist, bicuculline (5 microM, 10 microM, and 20 microM), adjacent to the recorded neurons via reverse microdialysis. Muscimol dose-dependently decreased the discharge of PF-LHA neurons including nonREM-off neurons. Muscimol-induced suppression of discharge during nonREM sleep was significantly weaker than the suppression produced during waking. In the presence of bicuculline, PF-LHA neurons, including nonREM-off neurons, exhibited elevated discharge, which was dose-dependent and was significantly higher during nonREM sleep, compared to waking. These results suggest that GABA(A) receptor mediated increased GABAergic tone contributes to the suppression of PF-LHA neurons, including nonREM-off neurons, during spontaneous nonREM sleep.
Alam
M N
MN
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA. noor@ucla.edu
Kumar
S
S
Suntsova
N
N
Bashir
T
T
Szymusiak
R
R
McGinty
D
D
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline