Project Summary/Abstract Animals have evolved specialized neural circuitry that links sensory input to neuroendocrine and behavioral responses. The proper function of these systems is essential for the health and wellbeing of individuals. Sensory inputs controls some fundamentally important innate behaviors, including mating, aggression and parental behaviors. Dysfunction in these circuits may lead to depression, mood disorders, sexual dysfunction, and aberrant parental behaviors. Here we propose to study the neural circuits that detect and process pheromone information and regulate endocrine and behavioral responses in rodents. In vertebrates, pheromone cues can directly trigger mating rituals and territorial aggression. Many terrestrial species have evolved highly sophisticated vomeronasal systems to detect pheromones. The vomeronasal circuit connects directly to the endocrine systems and influences their output. These circuits are largely genetically determined and there is an intrinsic link between sensory input and the behavioral responses. The mouse vomeronasal circuitry, therefore, serves as an ideal model system to elucidate the neural mechanism of sensory information processing, mechanism of neuroendocrine control and sensory control of innate behaviors. Similar circuits exist in humans but may have been compacted during primate evolution to consist of mostly the main olfactory system, and to include other sensory modalities. The study of the vomeronasal system can provide a roadmap to understand these more complex circuits. The objective of this application is to delineate the vomeronasal circuitry that detects and processes information of two classes of female pheromones. The proposal is based on our study identifying two sets of vomeronasal receptors recognizing pheromones cues that convey the sexual identity and the estrus status of female mice, respectively. In this study, we will determine the contribution of vomeronasal sensory neurons (VSNs) expressing these receptors to sexual behaviors. We will investigate and determine the connectivity diagram between the VSNs and the mitral cells in the accessory olfactory bulb. We will also identify the brain regions and specific cell populations that process information conveyed by these cues and map their connections. These studies are expected to reveal highly specific neural circuits that control mating behaviors