Characterization of mouse neuro-urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation.

Ito, Hiroki; Drake, Marcus J; Fry, Christopher H; Kanai, Anthony J; Pickering, Anthony E

AIM To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in vivo-like neural connectivity. METHODS Adult male mice were decerebrated and arterially perfused with a carbogenated, Ringer's solution to establish the DAPM. To allow distinction between central and peripheral actions of interventions, experiments were conducted in both the DAPM and in a "pithed" DAPM which has no brainstem or spinal cord control. RESULTS Functional micturition cycles were observed in response to bladder filling. During each void, the bladder showed strong contractions and the external urethral sphincter (EUS) showed bursting activity. Both the frequency and amplitude of non-voiding contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the LUT resulting in retention in DAPM as it increased tonic EUS activity and basal bladder pressure in a dose-dependent manner (basal pressure increase also noted in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion blockade (hexamethonium), initially caused incomplete voiding, and both drugs eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed bladder distention-induced activity in the non-noxious range which was associated with pMM. CONCLUSIONS This study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice.