. The proper function of the sensory and endocrine systems is essential for the health and well being of human beings. A set of fundamentally important innate behaviors, including mating and aggression, are controlled by sensory responses. Animals have evolved specialized neural circuitry that links sensory input to endocrine systems. Dysfunction in these circuits may lead to depression, mood disorders, sexual dysfunction and aberrant behaviors. The neural circuits that differentially regulate endocrine responses are not well defined and the complexity of sensory experiences makes it difficult to study the circuits in humans. In vertebrates, innate behaviors such as mating rituals and territorial aggression are elicited by pheromone cues. Many terrestrial mammalian species have evolved highly sophisticated vomeronasal systems that detect pheromones, elicit endocrine responses and control behavioral states. The vomeronasal circuit connects directly to the endocrine systems and influences their output. These circuits are largely genetically determined and there is an intrinsic link between sensory input and the behavior responses. Similar circuits exist in humans but may have been compacted during primate evolution to consist of mostly the main olfactory, and to include other sensory modalities. The mouse vomeronasal circuitry, therefore, serves as an ideal model system to elucidate the neural mechanism of sensory information processing, mechanism of neuroendocrine control and sensory control of innate behaviors. The objective of this application is to identify the neural circuitry that detect and process female pheromone information and delineate its function in eliciting male sexual behaviors. In the past, we have identified two sets of vomeronasal receptors that recognize pheromones cues that convey the sexual identity and the estrous status of female mice. We also purified these cues, which act synergistically to trigger mounting behavior in the males. In this study, we will identify the brain regions that process information conveyed by these cues and map their connections. We will genetically knock out the identified receptors to reveal their functional contribution to male mounting behavior. Moreover, we will functionally interrogate different brain regions activated by the pheromone cues to understand the contribution of distinct circuit components to male sexual behavior. These studies are expected to reveal highly specific neural circuits that control mating behaviors in the male animals. Insight gained from this study will help to elucidate control mechanism of endocrine systems and motivational states.

Public Health Relevance

. The proper functioning of the sensory and endocrine systems is crucial to the health and well being of humans. Social communications and the emotional well being are critically dependent on the proper processing of social information. Cognitive deficits in many psychiatric disorders are largely the results of defects in the brain circuits. The proposed study will allow us to understand the neural circuitry that mediates social communications among animals, which has a direct influence on the endocrine control of reproductive and aggressive behaviors. Elucidating the functional logic of this circuit will provide insights into the brain mechanisms for sensory information processing, social communications and endocrine control. This knowledge can be used for diagnostic and therapeutic applications.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008003-12
Application #
9352802
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
Sullivan, Susan L
Project Start
2006-01-10
Project End
2021-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
12
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Stowers Institute for Medical Research
Department
Type
DUNS #
614653652
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Duyck, Kyle; DuTell, Vasha; Ma, Limei et al. (2017) Pronounced strain-specific chemosensory receptor gene expression in the mouse vomeronasal organ. BMC Genomics 18:965
Haga-Yamanaka, Sachiko; Ma, Limei; Yu, C Ron (2015) Tuning properties and dynamic range of type 1 vomeronasal receptors. Front Neurosci 9:244
Kim, SangSeong; Ma, Limei; Unruh, Jay et al. (2015) Intracellular chloride concentration of the mouse vomeronasal neuron. BMC Neurosci 16:90
Yu, C Ron (2015) TRICK or TRP? What Trpc2(-/-) mice tell us about vomeronasal organ mediated innate behaviors. Front Neurosci 9:221
Haga-Yamanaka, Sachiko; Ma, Limei; He, Jie et al. (2014) Integrated action of pheromone signals in promoting courtship behavior in male mice. Elife 3:e03025
Yu, C Ron (2013) Calcium imaging of vomeronasal organ response using slice preparations from transgenic mice expressing G-CaMP2. Methods Mol Biol 1068:211-20
Kim, SangSeong; Ma, Limei; Jensen, Kristi L et al. (2012) Paradoxical contribution of SK3 and GIRK channels to the activation of mouse vomeronasal organ. Nat Neurosci 15:1236-44
Kim, SangSeong; Ma, Limei; Yu, C Ron (2011) Requirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons. Nat Commun 2:365
Ma, Limei; Haga-Yamanaka, Sachiko; Yu, Qingfeng Elden et al. (2011) Imaging neuronal responses in slice preparations of vomeronasal organ expressing a genetically encoded calcium sensor. J Vis Exp :
He, Jie; Ma, Limei; Kim, Sangseong et al. (2010) Distinct signals conveyed by pheromone concentrations to the mouse vomeronasal organ. J Neurosci 30:7473-83

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