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.

Public Health Relevance

The mechanisms underlying the integration of complex sensory inputs and leading to specific behavioral responses constitute a fundamental question in systems neuroscience. We are specifically interested in uncovering the neural principles underlying the central coding and processing of sensory cues leading to appropriate social or defensive responses. Because these principles are likely to be broadly shared across mammals, we expect the neural mechanisms uncovered in our studies to be largely applicable to human health and diseases, and to help understand the pathology of social and sensory communication disorders and guide therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC013087-05
Application #
9231422
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2013-03-20
Project End
2018-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
5
Fiscal Year
2017
Total Cost
$323,212
Indirect Cost
$131,962
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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