Characterization of neural circuits mediating social behavior

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): The vomeronasal system (VNS) detects important chemosensory cues in the local environment and transforms these cues into adaptive social behaviors. Despite myriad advances in our understanding of the cellular and molecular biology of the VNS, several essential questions remain unexplored, in particular concerning the electrophysiological properties of higher nuclei in the VNS. The studies described in this proposal are aimed at identifying neural computations occurring in the medial amygdala (MEA) that are critical for the transduction of sensory cues and generation of social behavior. Several convincing lines of anatomical, molecular, pharmacological, and behavioral evidence indicate that MEA neurons represent a critical stage for information processing within the VNS. The MEA receives sensory input from the accessory olfactory bulb, and is reciprocally connected with a network of nuclei essential for the production or social behaviors. The MEA is segregated into regions with distinct genetic expression patterns that delineate important functional segregations. For example, the posterior dorsal MEA (MEApd) is important for the detection of reproductive stimuli, while the posterior ventral MEA (MEApv) is specialized to detect defensive stimuli. Aromatase-expressing neurons, found in the MEApd but not in the MEApv, are sexually dimorphic in number and projection pattern, and are thought to underlie VNS mediated sexually dimorphic behaviors. The work outlined in the proposal will be performed over the next three years. The principle investigator will conduct the vast majority of the described experiments and data analyses. However, several key components of these experiments will be conducted in collaboration with members of the Dulac lab having relevant skill sets. Each aim of this proposal employs recording electrophysiological responses in the MEA while stimulating the VNS with ethologically important stimuli. Stimuli were chosen to encompass broad categories such as predators, mates, sympatric competitors, and kin. The purpose of the first specific aim is to systematically determine patterns of chemosensory responses present in the MEA. The second aim extends these findings by assigning specific response patterns to genetically defined populations of MEA neurons. The third aim, investigates the role of the MEA in guiding social behavior using electrophysiology in awake mice. These complimentary experimental approaches will provide important insights into the neural mechanisms that detect chemosensory cues and produce essential social behaviors. PUBLIC HEALTH RELEVANCE: Since aromatase inhibitors are rapidly becoming a first-line treatment for breast cancer, it is important to understand the normal function of aromatase signaling in the brain. The functional characterization of aromatase expressing neurons will likely provide important insights for the beneficial treatment of breast cancer.