Studies conducted under this grant are aimed at characterizing brain circuits underlying pheromone- evoked behaviors and endocrine responses in the mouse. Recent data has demonstrated the involvement of both olfactory and vomeronasal (VNO) systems in pheromone processing and the key role of VNO inputs in ensuring the sex specificity of behavioral responses. These findings raise two fundamental questions: how are olfactory and VNO inputs integrated in order for the animal to achieve physiologically relevant responses, and what is the respective role of each chemosensory system and associated receptors in pheromone processing. We will investigate the hypothesis that specific neuropeptide networks integrate both olfactory and VNO pheromone signals throughout the brain in order to mediate reproduction and aggressive responses. Conditional pseudorabies virus (PRV) and genetic manipulations will be used to trace circuits associated with peptidergic neurons involved in the control of reproduction and aggression, respectively, and to identify specific olfactory and vomeronasal areas and sensory receptors involved. The functional contribution of olfactory and VNO inputs to the uncovered circuits will be further investigated by targeted genetic ablations. These studies will provide critical insights into the mechanisms by which the brain integrates distinct sensory information to regulate the neuroendocrine axis and the expression of appropriate behaviors.

Public Health Relevance

Research and Related Other Project Information Project Narrative The identification of discrete populations of neurons across the brain that are specifically engaged in the control of reproduction and aggression should provide new and significant insights for the development of novel therapies related to fertility and the control of pathological aggressive behavior in mental diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009019-05
Application #
8481529
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$325,013
Indirect Cost
$131,553
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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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
Santoro, Stephen W; Dulac, Catherine (2012) The activity-dependent histone variant H2BE modulates the life span of olfactory neurons. Elife 1:e00070
Isogai, Yoh; Si, Sheng; Pont-Lezica, Lorena et al. (2011) Molecular organization of vomeronasal chemoreception. Nature 478:241-5
Dani, Adish; Huang, Bo; Bergan, Joseph et al. (2010) Superresolution imaging of chemical synapses in the brain. Neuron 68:843-56
Dulac, Catherine (2010) Brain function and chromatin plasticity. Nature 465:728-35