Genetic Mapping of Functional Vomeronasal Circuits

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7. Project Summary/Abstract. The proper function of the sensory and endocrine systems is essential for the health and well being of human beings. A set of fundamentally important innate behaviors, including mating and aggression, are controlled by sensory responses. Animals have evolved specialized neural circuitry that links sensory input to endocrine systems. Dysfunction in these circuits may lead to depression, mood disorders, sexual dysfunction and aberrant behaviors. The neural circuits that differentially regulate endocrine responses are not well defined and the complexity of sensory experiences makes it difficult to study the circuits in humans. In vertebrates, innate behaviors such as mating rituals and territorial aggression are elicited by pheromone cues. Many terrestrial mammalian species have evolved highly sophisticated vomeronasal systems that detect pheromones, elicit endocrine responses and control behavioral states. 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 behavior responses. Similar circuits exist in humans but may have been compacted during primate evolution to consist of mostly the main olfactory, and to include other sensory modalities. 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. The objective of this application is to identify the neural circuitry that detect and process female pheromone information and delineate its function in eliciting male sexual behaviors. In the past, we have identified two sets of vomeronasal receptors that recognize pheromones cues that convey the sexual identity and the estrous status of female mice. We also purified these cues, which act synergistically to trigger mounting behavior in the males. In this study, we will identify the brain regions that process information conveyed by these cues and map their connections. We will genetically knock out the identified receptors to reveal their functional contribution to male mounting behavior. Moreover, we will functionally interrogate different brain regions activated by the pheromone cues to understand the contribution of distinct circuit components to male sexual behavior. These studies are expected to reveal highly specific neural circuits that control mating behaviors in the male animals. Insight gained from this study will help to elucidate control mechanism of endocrine systems and motivational states.