PD19-07 CRH NEURONS OF BARRINGTON’S NUCLEUS ARE NECESSARY BUT NOT SUFFICIENT FOR CO-ORDINATED VOIDING IN MICE

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2018PD19-07 CRH NEURONS OF BARRINGTON’S NUCLEUS ARE NECESSARY BUT NOT SUFFICIENT FOR CO-ORDINATED VOIDING IN MICE Hiroki Ito, Marcus Drake, Christopher Fry, Anthony Kanai, and Anthony Pickering Hiroki ItoHiroki Ito More articles by this author , Marcus DrakeMarcus Drake More articles by this author , Christopher FryChristopher Fry More articles by this author , Anthony KanaiAnthony Kanai More articles by this author , and Anthony PickeringAnthony Pickering More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.997AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The pontine micturition centre (PMC) is thought to activate the sacral parasympathetic neurons controlling the detrusor and inhibit the somatic motoneurons of the external urethral sphincter (EUS). Many PMC neurons express corticotropin-releasing hormone (CRH) and a recent study using CRH-ires-CRE knock-in mice enabled opto- and chemo-genetic manipulation of their activity (Hou et al. Cell 2016). This indicated that the CRH neurons were glutamatergic, caused bladder contraction and an increase in the probability of micturition. We asked whether these CRH neurons alone could produce co-ordinated micturition. METHODS To target PMC in CRH-ires-CRE mice, stereotaxic injections of Cre-inducible vectors (AAV-EF1a-DIO-hChR2-mCherry or AAV-hSyn-DIO-hm4D-mcherry) to enabled light-activation or clozapine N-oxide (CNO)-induced neuronal silencing. Subsequently under urethane anaesthesia an optic fibre was placed above PMC for optogenetic stimulation. Bladder pressure was monitored with a PE-50 catheter and EUS-EMG was recorded with implanted electrodes. RESULTS The vectors allowed selective expression of ChR2/DREADD within CRH+ PMC neurons (Fig. 1a). Optogenetic activation of PMC-CRH neurons (473 nm, 5-30ms x 2.5-20Hz for 5s) reliably evoked transient non-voiding bladder contractions (“opto-NVCs”, 1.6 ? 0.4 mmHg, 20ms-pulse x 20Hz, n=9) of an empty bladder (Fig. 1b). Surprisingly there was little relationship between opto-stimulus parameters and opto-NVC amplitude unlike response probability. A comparison of opto-NVCs and spontaneous NVCs showed that the optogenetic activation did not activate the EUS. Opto-stimulation when the bladder was full could trigger voids. Chemogenetic inhibition of the PMC-CRH neurons with CNO (5ug/kg) reversibly inhibited voiding. CONCLUSIONS These data support the role of the PMC CRH neurons as being pre-parasympathetic neurons that are required for voiding but they are not part of EUS motor control. The PMC-CRH neurons are not high-fidelity controllers of micturition but they do influence timing of events. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e397-e398 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Hiroki Ito More articles by this author Marcus Drake More articles by this author Christopher Fry More articles by this author Anthony Kanai More articles by this author Anthony Pickering More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...