Disruption of Glomerular Map Formation in the Accessory Olfactory System Impairs Chemosensory Processing and Social...

Chemosensory signals play a fundamental role in guiding innate behaviors in mice, including mating, territoriality, and aggression, through specialized olfactory subsystems, such as the vomeronasal system. Chemosignals activate distinct subsets of glomeruli in the accessory olfactory bulb (AOB), suggesting that glomerular maps may contribute to the interpretation of chemosensory information driving these behaviors. Here, we investigate the consequences of altering glomerular map organization on sensory processing and social behavior in male and female mice by ablating the expression of the cell adhesion receptor Kirrel3 in basal vomeronasal sensory neurons (VSNs). Conditional ablation of Kirrel3 in VSNs led to a marked reorganization of the posterior AOB, characterized by altered specificity of VSN innervation and enlarged glomeruli. Despite retaining the ability to discriminate male from female urine, Kirrel3-deficient mice exhibited significantly reduced vomeronasal acuity to chemosignals, which is associated with a loss of male-directed aggression in both male and postpartum female mice. Functional mapping of neural activity revealed attenuated responses in mitral cells of the AOB, as well as in aggression-related brain regions, including the medial amygdala and ventromedial hypothalamus. These findings underscore the critical role of glomerular map integrity in the vomeronasal system for maintaining chemosensory acuity and regulating social behaviors. Furthermore, this study provides insight into how molecular disruptions in sensory neuron connectivity can reshape neural circuits and behavioral outputs.