Motor Cortex VIP Interneurons Participate in Dexmedetomidine-Associated Sleep Modulation.

Vasoactive intestinal peptide (VIP)-expressing neurons within the motor cortex (MC) exhibit diurnal variation in excitability and may participate in the modulation of sleep architecture. In this study, we found that MCVIP neurons displayed significantly higher excitability during the light phase. Using chemogenetic approaches, we examined their contribution to sleep-wake modulation. Given the sleep-modulating actions of the α2-adrenergic receptor agonist dexmedetomidine (Dex), we further tested whether Dex engages MCVIP neurons. Dex increased MCVIP neuronal excitability in slice recordings in an α2-adrenergic receptor-dependent manner. In addition, Dex suppressed spontaneous inhibitory postsynaptic current (sIPSC) frequency and increased excitatory synaptic drive onto MCVIP neurons. Critically, chemogenetic inhibition of MCVIP neurons attenuated Dex-associated prolongation of non-rapid eye movement (NREM) sleep. Together, these findings suggest that MCVIP neurons represent a cortical component associated with the temporal modulation of Dex-related sleep-state changes, and that α2-adrenergic receptor signaling contributes to the observed electrophysiological effects under the present slice-recording conditions.