GABA Receptors on Orexin and Melanin-Concentrating Hormone Neurons Are Differentially Homeostatically Regulated Following Sleep Deprivation.
Though overlapping in distribution through the hypothalamus, orexin (Orx) and melanin-concentrating hormone (MCH) neurons play opposite roles in the regulation of sleep-wake states. Orx neurons discharge during waking, whereas MCH neurons discharge during sleep. In the present study, we examined in mice whether GABAA and GABAB receptors (Rs) are present on Orx and MCH neurons and might undergo differential changes as a function of their different activities following sleep deprivation (SD) and sleep recovery (SR). Applying quantitative stereological image analysis to dual-immunofluorescent stained sections, we determined that the proportion of Orx neurons positively immunostained for GABAARs was significantly higher following SD (∼48%) compared with sleep control (SC; ∼24%) and SR (∼27%), and that the luminance of the GABAARs was significantly greater. In contrast, the average proportion of the MCH neurons immunostained for GABAARs was insignificantly lower following SD (∼43%) compared with SC (∼54%) and SR (56%), and the luminance of the GABAARs was significantly less. Although, GABABRs were observed in all Orx and MCH neurons (100%), the luminance of these receptors was differentially altered following SD. The intensity of GABABRs in the Orx neurons was significantly greater after SD than after SC and SR, whereas that in the MCH neurons was significantly less. The present results indicate that GABA receptors undergo dynamic and differential changes in the wake-active Orx neurons and the sleep-active MCH neurons as a function of and homeostatic adjustment to their preceding activity and sleep-wake state.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal, Quebec, Canada H3A 2B4.
Hanieh
H
Toossi
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal, Quebec, Canada H3A 2B4.
Esther
E
Del Cid-Pellitero
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal, Quebec, Canada H3A 2B4.
Barbara E
0000-0001-9985-3860
BE
Jones
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004569:Electroencephalography; D006706:Homeostasis / Q000502:physiology; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D000068797:Orexins / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000378:metabolism* / Q000473:pathology; D014851:Wakefulness / Q000502:physiology
D007028:Hypothalamic Hormones; D008543:Melanins; D000068797:Orexins; D010907:Pituitary Hormones; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C019463:melanin-concentrating hormone
GABAAR; GABABR; homeostasis; mice; waking