SST neurons in the periaqueductal gray regulate urination and bladder function

Abstract

Urination, a fundamental physiological process, is intricately regulated by central neural circuits. The periaqueductal gray (PAG) is a critical hub for urination control, yet the specific neuronal subtypes involved remain undefined. Here, we identified somatostatin (SST)-expressing neurons in the lateral and ventrolateral PAG (l/vlPAG) as key regulators of urination. SST+ neurons in the l/vlPAG exhibited activity closely aligned with urination onset in freely moving animals. Optogenetic activation of these neurons reliably triggered urination and bladder contraction, whereas their acute inhibition at urination onset halted ongoing urination. Moreover, activation of l/vlPAG SST+ neurons projecting to the pontine micturition center (PMC) elicited urination and bladder contraction, effects that were absent following pelvic nerve transection. These findings reveal that l/vlPAG SST+ neurons regulate urination through the PAG-PMC pathway, providing new insights into bladder control and potential therapeutic targets for bladder dysfunction.