Prior studies identify brain/spinal cord regions involved in controlling bladder function, but often do not resolve neuronal subpopulations or their specific connections. We seek to develop in mice a complete circuit map of the control of bladder filling and voiding. Prior work and our own preliminary data identified the Pontine Micturition Center (PMC) and its large population of corticotropin releasing hormone (CRH) positive neurons (PMC-CRH) as the likely driver neurons of voiding. Our data shows that PMC-CRH neurons stimulate conscious voiding and bladder contractions under anesthesia when fired opto- or chemo-genetically. Selective ablation of PMC-CRH (Cre-driven expression of dipthteria toxin) eliminates voiding and normal bladder contractions on cystometrogram (CMG). Finding that PMC-CRH are the key PMC neurons driving voiding, we hae sought neurons which connect to them and modulate their activity. We have linked PMC-CRH neurons and multiple other brain sites, including specific populations of neurons in the periaqueductal gray (PAG) and the lateral preoptic area and lateral hypothalamic area (LPOA and LHA).
