Central Control Circuit for Context-Dependent Micturition

Abstract

Precise control of urine release (micturition) serves an essential physiological function, as well as a critical role in social communication in many animals. Here we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a higher order micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) are electrophysiologically distinct from their Crh-negative neighbors and send glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with bladder filling, is sufficient to drive bladder contraction upon activation, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and changing activity of one of the revealed candidate input areas, the Medial Preoptic Area (MPOA), significantly modulates hierarchy-dependent micturition pattern. Taken together, our results indicate that PMC Crh-expressing neurons are the command output of the brainstem that controls urine release and, due to convergent inputs from diverse brain regions, are poised to act as the integrating center for context-dependent micturition behavior in mice. These results provide an anatomical and molecular entry point into dissecting the process in the central nervous system for context-dependent micturition behavior.