SUFU 2019: Role of Corticotropin Releasing Hormone in Mouse Micturition Behavior
The authors here showed that PMC neuron subtypes are critical for specific aspects of micturition behavior.
Micro-injections of adeno-associated viruses (AAVs) or Diphtheria Toxin subunit-A (DTA) were placed into anatomically defined regions of the mouse brain, enabling highly selective expression of proteins in target neuron populations. A novel non-invasive void-spot assay, micturition video thermography (MVT), was used to track voiding behavior in awake-behaving mice. MVT was combined with optogenetic and chemogenetic stimulation, conditional neuron ablation, brain site-specific gene knockout, and recording of neural population activity. Following MVT, manipulations were repeated while recording bladder pressure in behaving mice or under anesthesia.
Optogenetic stimulation of PMCVglut2neurons was sufficient to generate strong bladder contractions and voiding responses. Direct optogenetic stimulation of specifically PMCCrh/Vglut2somas also generated voiding responses, although surprisingly these responses were comparably modest. They used a genetically targeted approach to selectively ablate PMCCrh/Vglut2 or PMCVglut2neurons. Genetic ablation resulted in abnormal micturition behaviors. Subsequent specific disruption of CRH but not glutamate signaling in PMC neurons had no effect on voiding or voiding contractions. They recorded Ca2+fluorescence changes to study the timing of neural activity with respect to detrusor contraction and voiding and found that subpopulations have distinct activity patterns that may drive particular aspects of bladder control.
They were able to identify the molecular identity of PMC neurons with functional roles in controlling urinary voiding and continence. Their results further suggest that glutamatergic PMC neurons are necessary and sufficient in regulating bladder function. Though the PMCCrh/Vglut2subpopulation of glutamatergic PMC neurons plays a role in controlling bladder function and can serve as a convenient marker neuron population, the expression of CRH is not essential to the function of these neurons.
Presented by: Anne Verstegen, Department of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Authors: Anne Verstegen1, Nataliya Klymko1, Reina Kobayashi1, John Mathai1, Veronique VanderHorst2, Mark Zeidel1
Author Affiliation:
1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
2. Beth Israel Deaconess Medical Center, Neurology Department, Harvard Medical School
Written by: Bilal Farhan, MD, Clinical Instructor, Female Urology and Voiding Dysfunction, Department of Urology, University of California, Irvine @Bilalfarhan79 at the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting, SUFU 2019, February 26 - March 2, 2019, Miami, Florida