Manipulation of bladder contraction by cell-type selective optogenetics of the anterior cingulate cortex neurons in a mouse model with increased urinary frequency.

Abstract

Optogenetics is a powerful technique for both investigating the mechanism underlying neurological disorders and modifying them using disease model animals. However, there is limited evidence demonstrating the potential of optogenetics in disease (lower urinary tractdysfunction; LUTD) model with targetingthe cerebral cortex.Here, we evaluated the effect of optogenetic stimulation of GABAergic neurons intheanterior cingulate cortex (ACC) on urodynamics in a urinary frequency mouse model. Channelrhodopsin-2 (ChR2) was selectively expressed in parvalbumin expressing neurons of the ACC in mice. For the induction of urinary frequency, 0.1% acetic acid was perfused into the bladder, while normal saline was used for control. Photostimulation was delivered to the ACC and intercontraction intervals (ICIs) were measured before, during and after photostimulation. Photostimulation prolonged ICI only during stimulation and ICI was recovered after stimulation in control condition. We found in the urinary frequency model that photostimulation also significantly prolonged ICI, which was recovered after stimulation. Cell-type selective photoactivation in the ACC can modulate urodynamics in disease model. The application of optogenetics for the treatment of LUTD have an advantage of temporal specificity, making it useful for controlling immediate urgency.