Abstract
AimTo 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.MethodsAdult 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.ResultsFunctional 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.ConclusionsThis study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice.
Highlights
The micturition cycle consists of two-phases of bladder activity: filling and voiding
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
This study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice
Summary
The micturition cycle consists of two-phases of bladder activity: filling and voiding. This is achieved by the co-ordinated action of both the autonomic and somatic motor system. A spinalbrainstem-spinal loop is the core circuit controlling micturition including the periaqueductal gray and pontine micturition center (Barrington's nucleus). This circuit responds to afferent inputs from the bladder to generate voiding.[1,2] the neural mechanisms that generate and regulate the phases of micturition[1,2] have not been fully elucidated in man nor in animal models. A drawback of DAPR for some types of studies was the need to use young rats primarily due to the challenge of establishing adequate tissue perfusion in larger animals, which limited preparation viability
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