Bar neurons and urination

A newly identified subset of excitatory Barrington nucleus (Bar) neurons express oestrogen receptor 1 (ESR1) and control the urethral sphincter in mice. This discovery improves our understanding of the neuronal control of urination.

Immunostaining revealed a small subpopulation of ESR1-expressing Bar (Bar^ESR1) neurons in mice distinct from Bar neurons that express corticotropin-releasing hormone (CHC). Fluorescence assays in ESR1-Cre mice using a voluntary urination assay, in which male mice urinate in response to smelling female mouse odour, showed that increases in fluorescence correlated with urination events.

Infection of Bar^ESR1 neurons with an excitatory optogenetic protein, channelrhodopsin 2 (ChR2), showed that, on photostimulation, these neurons caused frequency-dependent urine volume release in freely moving male mice with no female odour stimulation. Photostimulation under anaesthesia caused urine voiding in 46% of Bar^ESR1–ChR2 mice, but only in 6% of Bar^CHC–ChR2 mice, none of which occurred during the photostimulus window. Photostimulation of filled bladders showed that peak pressure and end pressure were considerably reduced in Bar^ESR1–ChR2 mice, owing to abundant liquid release resulting in a sharp decrease in pressure. Photostimultated urine release coincided with a bursting pattern of sphincter activity; urine voiding was pulsatile during the periods. Analysis of data from surgically implanted pressure recorders showed that urethral sphincter bursting patterns corresponded with urination behaviour in response to female odour.

Conversely, infection of Bar neurons with an inhibitory chemogenetic receptor and treatment with its ligand caused reduced urination in response to female odour in Bar^ESR1 mice. Infection of Bar^ESR1 neurons with an optogenetic inhibitor reduced urination in response to female odour and stopped bursting activity during photoinhibition.

These results show that Bar^ESR1 neurons are essential for voluntary urinary and sphincter activity in mice. Translating these findings to humans could improve our understanding of voiding dysfunction.