Past, Present, and Future in the Study of Neural Control of the Lower Urinary Tract

Abstract

The neurological coordination of the lower urinary tract can be analyzed from the perspective of motor neurons or sensory neurons. First, sensory nerves with receptors in the bladder and urethra transmits stimuli to the cerebral cortex through the periaqueductal gray (PAG) of the midbrain. Upon the recognition of stimuli, the cerebrum carries out decision-making in response. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs) and UMNs coordinate storage and urination in the brainstem for synergic voiding. In contrast, LMNs, which originate in the spinal cord, cause muscles to contract. These neurons are present in the sacrum, and in particular, a specific neuron group called Onuf's nucleus is responsible for the contraction of the external urethral sphincter and maintains continence in states of rising vesical pressure through voluntary contraction of the sphincter. Parasympathetic neurons originating from S2-S4 are responsible for the contraction of bladder muscles, while sympathetic neurons are responsible for contraction of the urethral smooth muscle, including the bladder neck, during the guarding reflex. UMNs are controlled in the pons where various motor stimuli to the LMNs are directed along with control to various other pelvic organs, and in the PAG, where complex signals from the brain are received and integrated. Future understanding of the complex mechanisms of micturition requires integrative knowledge from various fields encompassing these distinct disciplines.

Keywords: Nervous system; Periaqueductal gray; Pons; Urination.

Fig. 1.

Pathways depicting the general outline of pelvic organ stimulating center and pelvic floor stimulating center. These are gross outlines omitting interconnections afferent pathways, and specific control centers for functions other than micturition.

Fig. 2.

Confocal image of expression of adeno-associated virus - channelrhodopsin-2 (AAV-ChR2) (green) and DAPI (4’,6-diamidino-2-phenylindole) (blue) at 3 weeks after AAV-ChR2 injection into the adult dentate gyrus (DG) shows incorporation of optogenetic modification to control detrusor overactivity in peripheral insult models, such as in interstitial cystitis/bladder pain syndrome [68].

Fig. 3.

Treadmill running model incorporated with optogenetic control of voiding centers. Such models show how conventional physiologic models of micturition can be complemented and incorporated with optogenetic studies [73].