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Sensory processing of social and defensive chemosignals

$359,125R01FY2016DCNIH

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): The goal of this project is to investigate how social chemosignals are processed by vomeronasal circuits in many species, the signals essential for guiding social interactions rely on the emission and detection of pheromones. Rodents strongly rely on the vomeronasal system to detect these cues and guide genetically pre-programmed social and defensive behaviors. We, and others, have recently made significant progress in understanding the molecular and celular basis of chemosensory detection by the vomeronasal organ (VNO) and in visualizing complex patterns of activity by its primary target, the accessory olfactory bulb (AOB). However, the information processing performed by downstream brain areas in order to elicit innate behavioral responses. encode behaviorally relevant signals has not yet been uncovered. This project draws on novel electrophysiological, genetic and optogenetic approaches to determine how units from the (MeA) transform social and defensive sensory cues into behavioraly relevant signals. The MeA occupies a critical position in the vomeronasal-sensorimotor transformation between the AOB and distinct nuclei of the hypothalamus that are involved in eliciting distinct behavioral responses. medial amydgala Proposed experiments will address 1- how the MeA processes the complex sensory representation from the AOB, in order to convey information reflecting the behavioral significance of the detected cues to centers in the hypothalamus. 2- the sensory representation of distinct genetically defined populations of neurons in the MeA, and more specifically the responses of two complementary populations of neurons expresing either the enzyme aromatase (Ar) or thyrotropin-releasing hormone (TRH that are located in distinct areas of the MeA reported to drive mating and defensive behaviors, respectively. 3- the contribution of elementary VNO signals to neuronal activation across the brain using transgenic mouse lines and optogenetic tools that enable the activation of discrete receptor populations corresponding to the detection of predators, as well as male and female conspecifics. In humans, defects in social recognition are the core of poorly understood and debilitating mental disorders such as autism and schizophrenia. Because of their central role in the coding and processing of environmental cues leading to appropriate behavioral responses, the neural principles of social and defensive recognition uncovered in these studies are largely applicable throughout the animal kingdom. Thus, our findings will inform the diagnosis and treatment of mental disorders, in which social and sensory communications are impaired.

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