0163 Investigating the Role of Vasoactive Intestinal Peptide-Containing Neurons of the Ventromedal Preoptic Area in Sleep-Wake Control

Abstract

Abstract Introduction A role for vasoactive intestinal peptide (VIP) in promoting rapid eye movement (REM) sleep has been suggested, but the anatomical location of the neurons that release VIP to promote REM sleep has not been identified. Here, we investigated the role of VIP-containing cell groups in the ventromedial preoptic area (VMPOVIP) in sleep-wake regulation. The VMPO has also previously been implicated in thermoregulation and the febrile response. Methods We first investigated the native firing activity of VMPOVIP neurons, over repeated sleep-wake cycles, using in vivo fiber photometry in VIP-ires-Cre mice. We next examined the afferent and efferent profile of this cell group using conditional retrograde (pseudotyped modified rabies) and anterograde (adeno-associated viral vector-based) tracers. We finally utilized a chemogenetic strategy to selectively activate VMPOVIP neurons cells while monitoring electroencephalogram/electromyogram activity and core body temperature, in order to determine their role in sleep-wake and thermoregulatory control. Results We found that VMPOVIP cells were predominantly and strikingly REM-active, that they received many synaptic inputs from surrounding hypothalamic regions (including the ventromedial hypothalamus, dorsomedial hypothalamus and the arcuate nucleus), and that they targeted established sleep-wake nodes, such as the ventrolateral preoptic nucleus, tuberomammillary nucleus, lateral hypothalamus and ventrolateral periaqueductal gray area. To our surprise, chemogenetic activation of the VMPOVIP cell population had little effect upon all measures of sleep-wake analysed and no effect upon core body temperature. Conclusion We conclude that VMPOVIP neurons do not promote REM sleep per se. However, their REM-active profile and anatomical connectivity suggest that these neurons may play a functional role in generating certain cardinal features of REM sleep, which is an active focus of on-going research in our laboratory. Support SRSF CDA #016-JP-17 to A.V. and NS073613, NS092652 and NS103161 to P.M.