“Descending Enkephalinergic neurons in Barrington’s nucleus gate sex-biased control of micturition”
- 1Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA USA
- 2University of Maryland School of Medicine, Baltimore, MD USA
Abstract
Barrington’s nucleus (Bar) is a brainstem hub essential for lower urinary tract (LUT) function, yet the molecular identity and functional specialization of its neuronal subtypes remain poorly defined. Here, we construct a single-nucleus transcriptional atlas of the murine Bar and identify an excitatory Penk-expressing population (Bar-Penk) critical for LUT regulation. Bar-Penk neurons are selectively active during voiding, when the external urethral sphincter (EUS) relaxes, and their optogenetic activation elicits time-locked suppression of EUS activity. Chemogenetic activation of these neurons induces a sex-specific, aberrant pattern of micturition, whereas targeted ablation impairs voluntary marking behavior in response to female cues. We observe multiple regions involved in visceromotor regulation and behavioral state control that project to Bar-Penk neurons, supporting their role as integrators of internal state and environmental context that drive urinary output. These findings provide new insights into the brainstem circuits that shape reflexive and voluntary micturition and highlight how discrete neuronal subtypes contribute to sexually dimorphic regulation of LUT function.
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BibTeX
@article{klymko2026descending,
title = {{“Descending Enkephalinergic neurons in Barrington’s nucleus gate sex-biased control of micturition”}},
author = {Nataliya Klymko and Andrea M. Sartori and Mihoko Leon and Cassandra N. Seifert and Richard Lee and John C. Mathai and Anne M. J. Verstegen},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77949-4},
url = {https://doi.org/10.1038/s41467-026-77949-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - “Descending Enkephalinergic neurons in Barrington’s nucleus gate sex-biased control of micturition”
AU - Nataliya Klymko
AU - Andrea M. Sartori
AU - Mihoko Leon
AU - Cassandra N. Seifert
AU - Richard Lee
AU - John C. Mathai
AU - Anne M. J. Verstegen
PY - 2026
DA - 2026/09/28
JO - Nature Communications
DO - 10.1038/s41467-026-77949-4
UR - https://doi.org/10.1038/s41467-026-77949-4
AB - Barrington’s nucleus (Bar) is a brainstem hub essential for lower urinary tract (LUT) function, yet the molecular identity and functional specialization of its neuronal subtypes remain poorly defined. Here, we construct a single-nucleus transcriptional atlas of the murine Bar and identify an excitatory Penk-expressing population (Bar-Penk) critical for LUT regulation. Bar-Penk neurons are selectively active during voiding, when the external urethral sphincter (EUS) relaxes, and their optogenetic activation elicits time-locked suppression of EUS activity. Chemogenetic activation of these neurons induces a sex-specific, aberrant pattern of micturition, whereas targeted ablation impairs voluntary marking behavior in response to female cues. We observe multiple regions involved in visceromotor regulation and behavioral state control that project to Bar-Penk neurons, supporting their role as integrators of internal state and environmental context that drive urinary output. These findings provide new insights into the brainstem circuits that shape reflexive and voluntary micturition and highlight how discrete neuronal subtypes contribute to sexually dimorphic regulation of LUT function.
SN - 2041-1723
ER -