The major goal of this proposal is to understand the mechanisms and the general principles involved in sensory information processing. The proper function of the sensory systems is crucial to our health and well being. Numerous neurological and psychiatric disorders, such as schizophrenia, autism, attention deficit hyperactivity disorder (ADHD) and depression, all manifest defects in sensory responses. Sensory deficit is also the earliest sign of Parkinson's and Alzheimer's diseases. The study of the sensory systems will enable us to understand how the brain functions and help us to use this knowledge for diagnostic and therapeutic applications. To achieve this goal, one must study the neural circuitry that detects and integrates sensory input and elicits distinct behavioral output. In vertebrates, innate behaviors such as mating rituals and territorial aggression are largely elicited by the detection of pheromone cues through the vomeronasal organ. These behaviors are robust and stereotyped and their expression critically depends on the correct identification of pheromones. The neural circuits involved in pheromone detection are largely genetically determined. There is an intrinsic link between sensory input and behavior responses in the vomeronasal system, making it an attractive and tractable circuitry to understand sensory processing. In this study, we test the hypothesis that sensory information is encoded in the pattern of activation by different pheromones in the sensory cells. This information is further represented in the brain by the topographic projection from these neurons to allow an animal to discriminate gender, strain and the social and reproductive status of other individuals. We will first develop transgenic animals expressing calcium indicators in the sensory neurons to identify cells that respond to specific pheromones. Combining fluorescent imaging, mouse genetics and molecular biology, we will then identify the pheromone receptor gene these cells express. Third, we will trace the information flow by mapping the vomeronasal pathway with genetic labeling experiments. Finally, we will genetically inactivate subpopulations of neurons in the vomeronasal pathway to elucidate their functional contribution to pheromone perception. This functional mapping of the vomeronasal circuit will provide insight into how the sensory system detects, parses and integrates information to elicit specific behaviors. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC008003-01
Application #
7020272
Study Section
Special Emphasis Panel (ZRG1-MDCN-K (58))
Program Officer
Davis, Barry
Project Start
2006-01-10
Project End
2010-12-31
Budget Start
2006-01-10
Budget End
2006-12-31
Support Year
1
Fiscal Year
2006
Total Cost
$397,500
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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