Brainstem neurons coordinate the bladder and urethral sphincter for urination

Urination, a vital and conserved process of emptying urine from the urinary bladder in mammals, requires precise coordination between the bladder and external urethral sphincter (EUS) that is tightly controlled by a complex neural network. However, the specific subpopulation of neurons that accounts for such coordination remains unidentified, limiting the development of target-specific therapies for certain urination disorders, for example, detrusor-sphincter dyssynergia. Here, we find that cells expressing estrogen receptor 1 (ESR1⁺) in the pontine micturition center (PMC) initiate voiding when activated and suspend ongoing voiding when suppressed, each at 100% reliability. Transection of the pelvic nerve does not impair PMC^ESR1+ neurons' control of the EUS via the pudendal nerve, whereas transection of the pudendal nerve does not impair their control of the bladder via the pelvic nerve. Anatomically, PMC^ESR1+ neurons consist of three distinct spinal-projection-based subpopulations: one targeting the sacral parasympathetic nucleus, one innervating the dorsal gray commissure, and a third that projects to both regions, thereby enforcing the coordination of bladder contraction and sphincter relaxation in a rigid temporal sequence. Thus, we identify a cell type in the brainstem that controls the bladder-urethra coordination for urination.