Dopamine modulation of glutamatergic signaling in C. elegans chemosensation

多巴胺对线虫化学感受中谷氨酸信号的调节

基本信息

批准号：
8401132
负责人：
Michael Y Chao
金额：
$ 10.25万
依托单位：
CALIFORNIA STATE UNIV SAN BERNARDINO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8401132
关键词：
Affect Allied Health Profession Animal Behavior Animal Model Animals Award Behavior Behavioral Biology Brain Brain region Caenorhabditis elegans California Chemicals Complex Data Development Dopamine Dopamine Receptor Drug Addiction Glutamate Receptor Glutamates Goals Grant Hispanics Homologous Gene Individual Institution Interneurons Light Logic Long-Term Depression Long-Term Potentiation Maps Master&apos s Degree Measures Medical Minority Modeling Molecular Molecular Genetics Nematoda Nervous system structure Neurobiology Neurons Neurotransmitters Octanols Organism Outcome Pathway interactions Pattern Pharmaceutical Preparations Play Process Productivity Property Recruitment Activity Regulation Research Role Science Sensory Signal Transduction Site Students Synapses Synaptic plasticity System Testing Underrepresented Minority Universities Vertebrates Work avoidance behavior base career driving behavior graduate student insight kainate neural circuit neurotransmission programs public health relevance receptor expression receptor function relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of the research proposed herein is to understand the underlying neural logic of dopaminergic modulation of animal behavior. Dopamine modulation of synaptic plasticity is central to the molecular and cellular mechanisms underlying behavioral alterations associated with drug addiction. A great deal of progress has been made in understanding how dopamine alters synaptic activity in certain regions of the brain. However, less is known about how dopamine targets multiple regions of the brain and coordinates behavioral changes in intact neural circuits and organisms. In the nematode Caenorhabditis elegans, we have found that chemosensory avoidance behavior, which utilizes AMPA/kainate-like glutamate receptors for excitatory neurotransmission, is modulated by dopamine. Based on the expression patterns of the dopamine and glutamate receptors involved, dopaminergic input to the neural circuit that drive this behavior likely occurs at multiple cellular foci. This behavior in C. elegans thus serves as a model for understanding how dopamine functions systemically at multiple sites of action to modulate animal behavior. My specific aims are: (1) To precisely characterize the expression and site of action of dopamine receptors in the well-characterized chemosensory avoidance neural circuit of C. elegans; and (2) To determine how dopamine regulates glutamatergic signaling at sensory to interneuron synapses in this neural circuit. These studies will provide insight into how modulatory neurotransmitters such as dopamine globally affect behavioral circuits. 1

描述（由申请人提供）：本文提出的研究的长期目标是了解动物行为的多巴胺能调节的潜在神经逻辑。多巴胺对突触可塑性的调节是与药物成瘾相关的行为改变的分子和细胞机制的核心。在了解多巴胺如何改变大脑某些区域的突触活动方面已经取得了很大进展。然而，人们对多巴胺如何靶向大脑的多个区域并协调完整神经回路和生物体的行为变化知之甚少。在线虫秀丽隐杆线虫中，我们发现化学感应回避行为利用 AMPA/红藻氨酸样谷氨酸受体进行兴奋性神经传递，受到多巴胺的调节。根据所涉及的多巴胺和谷氨酸受体的表达模式，驱动这种行为的神经回路的多巴胺能输入可能发生在多个细胞灶处。因此，线虫的这种行为可以作为了解多巴胺如何在多个作用位点系统性地发挥作用以调节动物行为的模型。我的具体目标是：（1）精确表征线虫化学感应回避神经回路中多巴胺受体的表达和作用位点； (2)确定多巴胺如何调节该神经回路中感觉到中间神经元突触的谷氨酸信号传导。这些研究将深入了解多巴胺等调节性神经递质如何在全球范围内影响行为回路。 1