GABAergic control of micturition within the periaqueductal grey matter of the male rat

Non-technical summary Even when the bladder is full, emptying can be deferred voluntarily until individuals find themselves in a socially appropriate environment. This indicates that the brain is important in the control of bladder function. This study used drugs that either mimic or block the effects of the neurotransmitter chemicals involved in communication between nerve cells to investigate the brain nerve circuits that govern the control of the bladder. A small region in the midbrain was shown to be critical for normal bladder emptying to occur. Normally the excitability of the nerve circuits in this region was controlled by the action of an inhibitory neurotransmitter chemical called GABA. However, if GABA's effect was removed, bladder emptying became abnormally frequent. These results advance our understanding of the normal control of bladder function, and have implications for the development of new treatments for some forms of incontinence.In urethane-anaesthetised rats continuous infusion of saline into the bladder (6 ml h-1) evoked periodic sharp rises in intravesicular pressure accompanied by rhythmic bursting of external urethral sphincter (EUS) EMG and expulsion of urine from the urethral meatus. Microinjection of the GABA agonist muscimol (250 pmol) into the caudal ventrolateral periaqueductal grey (PAG), but not at other sites in the PAG, either depressed reflex voiding frequency (-60%, n = 7) and tonic EUS EMG activity (-38%, n = 6) or completely inhibited voiding (four sites). Microinjection of the GABA antagonist bicuculline (BIC; 1 nmol) into the same region, to reduce ongoing GABA tone, increased reflex voiding frequency (+467%, n = 16) and tonic activity in the EUS (+56%, n = 7) whilst bursting activity in the EUS became desynchronised. Although muscimol failed to change reflex micturition when microinjected into the dorsal caudal PAG, microinjection of BIC at these sites evoked pronounced autonomic arousal and increased reflex voiding frequency (+237%, n = 34). The results demonstrate that the functional integrity of synapses in the caudal ventrolateral PAG is essential to permit micturition. Transmission through the region is normally regulated by a tonic GABAergic inhibitory influence. In contrast, the functional integrity of the dorsal caudal PAG is not essential for reflex micturition. However, micturition may be initiated from this region via projections to the caudal ventrolateral PAG, as part of the behavioural response to psychological threat or other stressful stimuli.