Changes in excitability of midbrain micturition control circuitry during alterations in sleep-like brain states in rats – implications for nocturnal enuresis

Abstract

In humans micturition typically does not occur during sleeping but the bladder may accumulate a large volume of urine, which during wakefulness would be suprathreshold for triggering a need to void. The mechanism underlying this effect is not known but could include inhibition of sensory input from the bladder during sleep and/or a resetting of the excitability of the micturition control circuit. Micturition requires the functional integrity of a spino-midbrain-spinal loop that relays in the caudal ventrolateral periaqueductal grey (vlatPAG). We investigated whether the excitability of the micturition circuitry within the vlatPAG changed with arousal state. The urethane anaesthetised rat preparation was used, which shows spontaneous cyclical changes in EEG waveform that resemble changes in sleep state in unanesthetised animals. During infusion of saline into the bladder (6ml h−1) we found that transition from ‘arousal’ (desynchronised, low amplitude high frequency (3-5Hz) EEG) to synchronized high amplitude, slow wave (1Hz) activity (slow wave ‘sleep’) was accompanied by increases in micturition bladder pressure threshold and voided volume, and decreased end filling compliance, typical of natural sleep. The spontaneous firing of single units in the vlatPAG also slowed (8.0±3.2-3.0±1.9 Hz, n=15, p<0.01). These included 7 ‘micturition control’ neurons, which showed phasic changes in firing time-locked to changes in bladder pressure or external urethral sphincter EMG activity that were also depressed (n=6) or completely abolished (n=1) during SWS-like EEG activity. The results suggest that the micturition reflex is reset centrally during sleep. Failure of this mechanism could contribute to the development of nocturnal enuresis.