Voluntary urination control by brainstem neurons that relax the urethral sphincter

Voluntary urination ensures that waste is eliminated when safe and socially appropriate, even without a pressing urge. Uncontrolled urination, or incontinence, is a common problem with few treatment options. Normal urine release requires a small region in the brainstem known as Barrington’s nucleus (Bar), but specific neurons that relax the urethral sphincter and enable urine flow are unknown. Here we identify a small subset of novel Bar neurons that control the urethral sphincter in mice. These excitatory neurons express estrogen receptor 1 (Bar(ESR1)), project to sphincter-relaxing interneurons in the spinal cord and are active during natural urination. Optogenetic stimulation of Bar(ESR1) neurons rapidly initiates sphincter bursting and efficient voiding in anesthetized and behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals their necessity in motivated urination behavior. The identification of these cells provides an expanded model for the control of urination and its dysfunction.