In the rat, stimulation of bladder afferents during filling activates a spino-midbrain-spinal micturition reflex pathway that relays in the periaqueductal grey (PAG) (DeGroat, 2006). The pathway is normally subject to descending control from higher centres, so that voiding is “permitted” only when the individual is in a safe and socially acceptable environment. We have shown that a tonic GABAergic inhibition is imposed on the pathway at the level of the caudal ventrolateral PAG (caudal vlat PAG) (Stone et al., 2009). To enable urine to pass through the urethra, there must be synchronised activity between the detrusor and the external urethral sphincter (EUS). We have investigated the relationship between detrusor and EUS activity in the rat during voiding and examined midbrain influences. Experiments were carried out on urethane anaesthetised (1.4g/Kg i.p.) male Sprague-Dawley rats instrumented to record femoral arterial pressure, heart rate and tracheal airflow. A cannula inserted through the dome of the bladder was used to measure intravesicular pressure and to infuse saline. Bipolar stainless steel needle electrodes were inserted into the EUS to record EMG. Under resting conditions with the bladder partially filled, tonic activity was present in the EUS. Increases in intravesicular pressure evoked by external pressure on the bladder or by stepped infusion of saline triggered a phasic increase in EUS activity. Continuous infusion of saline in to the bladder (6ml h-1) induced periodic (0.73±0.04min-1, mean ± S.E.M) increases in bladder pressure accompanied by voiding. During filling, intravesicular pressure rose steadily but once a threshold was attained (15.20±0.38 mmHg), there was a sudden phasic increase in pressure (32.59±0.58mmHg) and a sharp increase in EUS-EMG activity, which adopted a bursting pattern whilst spurts of urine exited the penis. Following inactivation of the caudal vlatPAG by unilateral microinjection of muscimol (250pmol) whilst continuing to infuse saline, the level of tonic activity in the EUS decreased and the cycle of voiding slowed down (from 0.93±0.12 to 0.33±0.07 min-1, n=8) or ceased completely (n=3). Following microinjection of the GABAA antagonist bicuculline (1nmol) into the caudal vlatPAG, both the tonic activity in the EUS and the frequency of bladder contractions increased (from 0.69±0.08 to 1.86±0.63 min-1, n=15) but the synchronised bursting activity in the EUS during bladder contractions was disrupted. The results indicate that 1) Descending activity from the caudal vlatPAG determines the level of resting tone in the EUS. 2) The midbrain may contain a pattern generator, which is dependent on the functional integrity of local GABA-mediated events to initiate bursting activity of the EUS to produce spurting of urine output during voiding.