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bioRxiv · 10.64898/2026.07.23.736864

A Neuroendocrine Circuit That Suppresses Excretion and Pelvic Pain During Activity

Cabrera-Zapata, L. E.·Venkataraman, A.·Harrington, A. M.·Hu, J.·Castro-Navarro, F.·Galatsis, K.·Duan, X.·Brierley, S. M.·Keil Stietz, K.·Ingraham, H. A.
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Abstract

Mate-seeking during peak sexual receptivity is tightly coupled with exploratory movement, a process made more efficient by transient suppression of excretion. Here, we define a functional hypothalamic-hindbrain circuit in mice that promotes locomotion while eliminating urination and defecation for hours. Chemogenetic stimulation of excitatory estrogen-melanocortin-responsive MC4R+ neurons in the ventrolateral ventromedial hypothalamus (VMHvl) effectively silences bladder and colonic visceral reflexes, even at noxious distension pressures, underscoring the potency of this anti-excretion circuit. Pelvic sensations and excretion are restored only after ablating inhibitory GABAergic neurons in the Barringtons nucleus/locus coeruleus (BAR/LC) hindbrain region or after antagonizing endogenous endorphin signaling. Our study illustrates how a hormone-responsive brain node prioritizes movement over excretion and blunts pelvic discomfort, thereby optimizing an essential voluntary behavior for evolutionary fitness.

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Cabrera-Zapata, L. E., Venkataraman, A., Harrington, A. M., Hu, J., Castro-Navarro, F., Galatsis, K., Duan, X., Brierley, S. M., Keil Stietz, K., Ingraham, H. A.. 2026-07-27. A Neuroendocrine Circuit That Suppresses Excretion and Pelvic Pain During Activity. https://doi.org/10.64898/2026.07.23.736864

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