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 #
5R01DC013087-03
Application #
8803784
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2013-03-20
Project End
2016-02-29
Budget Start
2015-03-01
Budget End
2016-02-29
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
Kohl, Johannes; Dulac, Catherine (2018) Neural control of parental behaviors. Curr Opin Neurobiol 49:116-122
van der Linden, Carl; Jakob, Susanne; Gupta, Pooja et al. (2018) Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice. Nat Commun 9:5081
Li, Ying; Mathis, Alexander; Grewe, Benjamin F et al. (2017) Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice. Cell 171:1176-1190.e17
Yao, Shenqin; Bergan, Joseph; Lanjuin, Anne et al. (2017) Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues. Elife 6:
Kohl, Johannes; Autry, Anita E; Dulac, Catherine (2017) The neurobiology of parenting: A neural circuit perspective. Bioessays 39:1-11
Dulac, Catherine; O'Connell, Lauren A; Wu, Zheng (2014) Neural control of maternal and paternal behaviors. Science 345:765-70
Bergan, Joseph F; Ben-Shaul, Yoram; Dulac, Catherine (2014) Sex-specific processing of social cues in the medial amygdala. Elife 3:e02743
Wu, Zheng; Autry, Anita E; Bergan, Joseph F et al. (2014) Galanin neurons in the medial preoptic area govern parental behaviour. Nature 509:325-30