Probing Causality of the Brainstem-Hypothalamic Murine Models of Sleep-Wake Regulation

Abstract Sleep-wake regulation is thought to be governed by interactions among several nuclei in midbrain, pons, and hypothalamic regions. Determination of the causal role of these nuclei in state transitions requires simultaneous measurements from the nuclei with sufficient spatial and temporal resolution. We obtained long-term experimental single- and multi-unit measurements simultaneously from multiple nuclei of the putative hypothalamic and brainstem sleep-wake regulatory network in freely behaving rats. Cortical and hippocampal activity, along with head acceleration were also acquired to assess behavioral state. Here, we confirm that the general activity profile of the recorded sleep-wake regulatory nuclei is similar to the patterns presented previously in brief recordings of individual nuclei in head-fixed animals. However, we found that these activity profiles when studied with respect to cortical and behavioral signs of state transitions differ significantly from previous reports. Our findings pose fundamental questions about the neural mechanisms that maintain specific states and the neural interactions that lead to the emergence of sleep-wake states.