Urodynamic function during sleep-like brain states in urethane anesthetized rats

J Crook,T Lovick

doi:10.1016/j.neuroscience.2015.11.027

Abstract

The aim was to investigate urodynamic parameters and functional excitability of the periaqueductal gray matter (PAG) during changes in sleep-like brain states in urethane anesthetized rats. Simultaneous recordings of detrusor pressure, external urethral sphincter (EUS) electromyogram (EMG), cortical electroencephalogram (EEG), and single-unit activity in the PAG were made during repeated voiding induced by continuous infusion of saline into the bladder.The EEG cycled between synchronized, high-amplitude slow wave activity (SWA) and desynchronized low-amplitude fast activity similar to slow wave and ‘activated’ sleep-like brain states. During (SWA, 0.5–1.5Hz synchronized oscillation of the EEG waveform) voiding became more irregular than in the ‘activated’ brain state (2–5Hz low-amplitude desynchronized EEG waveform) and detrusor void pressure threshold, void volume threshold and the duration of bursting activity in the external urethral sphincter EMG were raised. The spontaneous firing rate of 23/52 neurons recorded within the caudal PAG and adjacent tegmentum was linked to the EEG state, with the majority of responsive cells (92%) firing more slowly during SWA. Almost a quarter of the cells recorded (12/52) showed phasic changes in firing rate that were linked to the occurrence of voids. Inhibition (n=6), excitation (n=4) or excitation/inhibition (n=2) was seen. The spontaneous firing rate of 83% of the micturition-responsive cells was sensitive to changes in EEG state. In nine of the 12 responsive cells (75%) the responses were reduced during SWA.We propose that during different sleep-like brain states changes in urodynamic properties occur which may be linked to changing excitability of the micturition circuitry in the periaqueductal gray.

Highlights

During the sleeping period urine production normally decreases compared to the waking state
These are defined by characteristic changes in the electroencephalogram (EEG) waveform, which cycles between low frequency, synchronized high-amplitude activity and high frequency, desynchronized, lowamplitude activity known as desynchronized or rapid eye movement (REM) sleep
The micturition reflex failed to establish In 11 animals (31%). In these rats bladder pressure rose during the infusion of saline until the animal entered a state of ‘‘overflow incontinence” during which bladder pressure remained high and fluid dripped from the penis at regular intervals

Summary

INTRODUCTION

During the sleeping period urine production normally decreases compared to the waking state. Under urethane anesthesia rats show spontaneous changes in the EEG that resemble slow wave and REM brain sleep states seen in unanesthetized animals (Clement et al, 2008). The urethane-anesthetized preparation has been used as a model to investigate central mechanisms underlying sleep Another feature of urethane anesthesia is that the micturition reflex is preserved, unlike other commonly used anesthetics (Yoshiyama et al, 2013). This preparation offers the advantage of investigating urodynamics and basic central control mechanisms of micturition during different sleep-like brain states more than in chronically instrumented, unanesthetized animals.

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION