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Glutamate-Mediated Neurotransmission and the Control of Behavior

谷氨酸介导的神经传递和行为控制

基本信息

批准号：
9128053
负责人：
Andres Villu Maricq
金额：
$ 32.59万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9128053
关键词：
Action Potentials Animal Model Autistic Disorder Behavior Behavior Control Behavioral Assay Bilateral Caenorhabditis elegans Calcium Chemotaxis Complex Deletion Mutation Development Disease Electrophysiology (science)Exhibits Genetic Genetic Polymorphism Glutamate Receptor Glutamates Goals Health Imaging Techniques Injection of therapeutic agent Interneurons Label Learning Link Location Maps Measures Mediating Medicine Mental Depression Mental disorders Modality Modeling Molecular Mutate Nervous system structure Neurobiology Neurologic Neurons Neurosciences Neurotransmitters Organism Process Property Research Role Schizophrenia Sensory Signal Transduction Stimulus Synapses Techniques Testing Time Vertebrates Work base gene product glutamatergic signaling in vivo imaging insight kainate mutant nervous system disorder neural circuit neurotransmission novel novel diagnostics novel therapeutics optogenetics postsynaptic presynaptic receptor receptor function research study response selective expression sensory input voltage

项目摘要

DESCRIPTION (provided by applicant): A major goal of neurobiology is to understand the control of behavior by neural circuits at the molecular level. This is also a major goal of clinica medicine as an increasing number of genetic polymorphisms associated with disorders such as autism, schizophrenia and depression suggest altered function of neural circuits. We propose molecular-based studies that will begin to elucidate the function of an experimentally accessible neural circuit in the genetically tractable model organism C. elegans. In preliminary experiments, we have demonstrated that this circuit has a general role in controlling navigation by C. elegans along gradients of sensory information. Many neurons in this circuit use the neurotransmitter glutamate, which activates multiple classes of postsynaptic ionotropic glutamate receptors (iGluRs) expressed in a single pair of interneurons. Interestingly, mutating these iGluRs has different effects on navigation during taxis behaviors. Furthermore, glutamate elicits complex action potentials and regional intracellular Ca2+ transients. The goals of our research are to provide mechanistic insights into how distinct sensory inputs to specific interneurons are transduced by different classes of postsynaptic iGluRs to modify electrical activity and thus control navigation. We will evaluate postsynaptic currents, electrical behavior and calcium transients in different mutant backgrounds, and link these parameters to how C. elegans navigates gradients of sensory information. In these studies, we will precisely map presynaptic sensory inputs to specific downstream interneurons and, using optogenetic strategies, determine how these inputs are integrated to control navigation. Our studies will provide a detailed molecular-based understanding of circuit function that can be used to generate testable hypotheses in more complex vertebrate circuits. We predict that what we learn from our proposed studies will have immediate relevance to ongoing studies of glutamatergic neurotransmission and the control of circuit function in vertebrates. Thus, our studies could contribute to new diagnostic or therapeutic modalities for neurological or psychiatric disorders associated with altered circuit function.