Regulation of Vomeronasal Stimulus Access by Cholinergic Solitary Chemosensory Cells in Mice

The vomeronasal organ (VNO) in the nasal cavity provides chemical sensory information to guide animal’s innate social and reproductive behaviors as well as predator and prey interactions. The access of stimulus fluids to the VNO relies on vasomotor movement of the vomeronasal cavernous vessels, which are controlled by the autonomic nervous system. Little is known about whether and how chemical constituents in the stimulus fluids are monitored to regulate their access. Using immunolabeling and transgenic mice, we identified a dense population of solitary chemosensory cells (SCCs) at the vomerosasal entry duct. These SCCs are trigeminally innervated, express transient receptor potential channel M5 (TRPM5) and phospholipase C (PLC) signaling pathway. Additionally, the SCCs express choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) for synthesizing and packaging acetylcholine. In single-cell Ca²⁺imaging experiments, SCCs respond to various chemicals including bitter-tasting compounds and odorous irritants primarily via the PLC pathway. To investigate further the role of SCCs in regulating VNO stimulus access, we developed a quantitative dye assay to determine the amount of stimulus fluid entering the VNO in freely behaving mice. We found that in wild type mice, the amount of the fluid entered is inversely correlated to the concentration of irritants and bitter substances in the fluid. In TRPM5 knockout mice, significantly larger amounts of bitter compounds enter the VNOs, showing impaired regulation of stimulus access. Moreover, two-week exposure to a bacterial toxicant results in defect predator odor-evoked fear reaction in TRPM5 knockout, but not in the wild type animals. Taken together, our data uncovered the essential role of SCCs in regulating vomeronasal vasomotor movement, hence stimulus access to the VNO. Our results also provide new insight into the emerging role of SCCs in chemoreception and regulation of physiological actions.