MP85-06 BRAIN NETWORKS CONTROLLING BLADDER FILLING AND VOIDING

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I1 Apr 2017MP85-06 BRAIN NETWORKS CONTROLLING BLADDER FILLING AND VOIDING Hanneke Verstegen, John Mathai, Mark Zeidel, and Joel Geerling Hanneke VerstegenHanneke Verstegen More articles by this author , John MathaiJohn Mathai More articles by this author , Mark ZeidelMark Zeidel More articles by this author , and Joel GeerlingJoel Geerling More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2668AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lower urinary tract symptoms (LUTS) are common and poorly understood; treatment is often ineffective. Failure of neural control of bladder function likely contributes to LUTS symptoms in many patients. Prior studies have shown that the pontine micturition center (PMC) directly controls voiding. Within the PMC corticotropin releasing hormone neurons (PMCCRH) project axons directly to spinal sacral cord nuclei that control bladder contraction. Here we show that PMCCRH neurons are critical for voiding, and identify neurons, particularly in the ventrolateral periaqueductal gray (PAGVL) which directly modulate PMCCRH and alter voiding. METHODS We inject adeno-associated viruses expressing proteins in a Cre-dependent fashion into anatomically defined regions of mice expressing Cre recombinase in specific neural types, to cause highly selective expression of these probes in target neuron populations. We monitor conscious voiding with micturition video thermography (MVT), and CMG under anesthesia while monitoring/stimulating specific neuron groups. RESULTS Stimulating PMCCRH neurons using designer receptors exclusively activated by designer drugs (DREADDs) produces urinary frequency in awake mice and on anesthetized CMG. Also, ablating PMCCRH neurons by selective expression of diphtheria toxin A disrupts normal voiding and the normal CMG voiding reflex. To identify neurons which provide input to PMCCRH, we used modified rabies virus and cholera toxin B labeling of PMCCRH and confirmed our results with viral anterograde tracing. Afferents to PMCCRH are located in PAGVL, the preoptic area, the lateral hypothalamic area, and other sites. Because sacral afferents sensing bladder filling project to PAGVL we determined the impact of stimulating Glutamatergic or GABA-ergic neurons (PAGVLGLUT or PAGVLGABA) in this region. Chemogenetic or optogenetic stimulation of PAGVLGLUT neurons leads to voiding and detrusor contraction. By contrast, chemogenetic or optogenetic activation of PAGVLGABAinhibits voiding and delays detrusor contraction on CMG. CONCLUSIONS 1. PMCCRH are driver neurons for detrusor contraction/voiding. 2. PAGVLGLUT project to PMCCRH, and when fired drive voiding/detrusor contraction. 3. PAGVLGABA project to PMCCRH and inhibit voiding/detrusor contraction. PAGVL, which receives bladder-based sacral afferents, likely controls bladder filling, and is a potential target in efforts to control urge incontinence and urgency symptoms of LUTS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1150 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Hanneke Verstegen More articles by this author John Mathai More articles by this author Mark Zeidel More articles by this author Joel Geerling More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...