TY - JOUR T1 - GABA Receptors on Orexin and MCH Neurons are Differentially Homeostatically Regulated following Sleep Deprivation JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0077-16.2016 SP - ENEURO.0077-16.2016 AU - Hanieh Toossi AU - Esther del Cid-Pellitero AU - Barbara E. Jones Y1 - 2016/06/01 UR - http://www.eneuro.org/content/early/2016/05/31/ENEURO.0077-16.2016.abstract N2 - 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%) as compared to 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%) in comparison to 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 sleep-active, MCH neurons as a function of and homeostatic adjustment to their preceding activity and sleep-wake state.Significance Statement: The activity of single neurons is regulated in a homeostatic manner such that prolonged activity results in decreased excitability. Orexin neurons discharge during waking, whereas MCH neurons do so during sleep. Here, we examined whether the inhibitory GABA receptors (Rs) on Orexin and MCH neurons would change differentially as a function of their different activities following sleep deprivation and sleep recovery. Whereas GABAAR and GABABR immunostaining appeared to increase on Orexin neurons, it appeared to decrease on MCH neurons after sleep deprivation relative to sleep control and sleep recovery. GABA receptors thus undergo differential changes on Orx and MCH neurons as a function of and homeostatic adaptation to their different activities during waking and sleep. ER -