Central Control Circuit for Context-Dependent Micturition

Abstract

SUMMARY Urine release (micturition) serves an essential physiological function as well as a critical role in social communication in many animals. Here we show a combined effect of olfaction and social hierarchy on micturition patterns in adult male mice, confirming the existence of a micturition control center that integrates pro- and anti-micturition cues. Furthermore, we demonstrate that a cluster of neurons expressing corticotropin-releasing hormone (Crh) in the pontine micturition center (PMC) are electrophysiologically distinct from their Crh-negative neighbors and send glutamatergic projections to the spinal cord. The activity of PMC Crh-expressing neurons correlates with and is sufficient to drive bladder contraction, and when silenced impairs micturition behavior. These neurons receive convergent input from widespread higher brain areas that are capable of carrying diverse pro- and anti-micturition signals, and whose activity modulates hierarchy-dependent micturition. Taken together, our results indicate that PMC Crh-expressing neurons are likely the integration center for context-dependent micturition behavior.

Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism

“…We previously demonstrated the use of our STPT pipeline for automated analysis of behavior-driven c-fos induction or anatomical anterograde or retrograde tracing (Hou et al, 2016; Jeong et al, 2016; Kim et al, 2016; Kim et al, 2015; Ragan et al, 2012). The use of this platform for quantitative brainwide mapping of cell type distribution represents a dramatic methodological advancement compared to laborious stereological methods (Schmitz and Hof, 2005) or the isotropic fractionator that can only analyze larger brain structures and does not preserve the spatial information (Herculano-Houzel et al, 2015).…”

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

“…Mutant males showed a greater hindquarter fall and increased micturition frequency compared with the female group. As expected, male mice urinate throughout the cage as a territorial marking, whereas females limit micturition to restricted zones . Furthermore, female mutant bapa mice presented a diminished tail squeeze compared with the female BALB/cJ.…”

Barrington's nucleus: Neuroanatomic landscape of the mouse “pontine micturition center”

“…Bar is a neuroanatomically defined population of neurons, which may participate in micturition and possibly other functions, while PMC refers less specifically to a functional hypothesis about this region and incorporates an as‐yet unsubstantiated assumption that neurons here function primarily or exclusively in micturition. Despite some evidence that Bar CRH neurons are involved in PMC function (Hou et al, ), there may not be a simple, one‐to‐one relationship between Bar (or Bar CRH ) neurons and the older term “PMC.” In fact, Bar CRH neurons are activated equally by distending the distal colon or bladder (Rouzade‐Dominguez et al, ), appear to innervate all pelvic visceral motoneurons in the sacral IML (above), and may modulate pelvic functions beyond just micturition (Holstege, ).…”

“…The efficiency of Cre‐reporters is sometimes less than ideal (Liu et al, ) and it is possible that not every Bar CRH neuron produces GFP, but in our experience labeling in this strain is consistent litter to litter, across age and gender. Our report provides a roadmap to the location and distribution of neurons accessible in physiology experiments using Crh‐IRES‐Cre mice to target Bar CRH neurons, which was the primary goal of this study (see also Hou et al, ).…”

“…This region is located between the locus coeruleus (LC) and laterodorsal tegmental nucleus (LDT) and contains a small number of neurons that increase their activity in response to bladder distention (Rouzade‐Dominguez, Pernar, Beck, & Valentino, ). Immediately before the bladder contracts, these neurons begin firing, and they sustain this activity throughout the contraction and in close correspondence to bladder pressure (Hou et al, ; Tanaka et al, ). Injecting electric current or glutamate in this region triggers micturition (Kruse, Mallory, Noto, Roppolo, & de Groat, ; Mallory, Roppolo, & de Groat, ; Mallory & Steers, ; Nishizawa, Sugaya, Noto, Harada, & Tsuchida, ; Sugaya, Matsuyama, Takakusaki, & Mori, ), while inhibition of or injury to this region prevents voiding, causing urinary retention in rats, cats, and humans (Barrington, ; Komiyama, Kubota, & Hidai, ; Mallory et al, ; Satoh, Shimizu, et al, 1978).…”