Synaptic mechanisms in the auditory system

听觉系统中的突触机制

基本信息

批准号：
7905764
负责人：
LAURENCE O TRUSSELL
金额：
$ 37.54万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7905764
关键词：
Acoustics Action Potentials Address Arts Auditory Auditory system Bicarbonates Brain Brain Stem Brain region Ca(2+)-Transporting ATPase Cell Line Cell membrane Cells Cochlear nucleus Complement Data Disease Drug Delivery Systems Exhibits Genetic Glutamates Glycine Glycine Receptors Golgi Apparatus Green Fluorescent Proteins Hearing problem Image Immunohistochemistry Knowledge Label Link Measurement Measures Mediating Microscopy Modeling Modification Mus Neurons Neurotransmitters Pathway interactions Phenotype Photons Play Process Property Reaction Time Regulation Relative (related person)Role Shapes Signal Transduction Slice Speed Synapses Synaptic Cleft System Testing Time Vesicle cell type clinically relevant compare effectiveness dorsal cochlear nucleus driving force excitatory neuron gamma-Aminobutyric Acid glycine transporter inhibitory neuron novel postsynaptic presynaptic protein expression receptor reconstruction research study response response to injury stellate cell synthetic enzyme tool transmission process voltage clamp

项目摘要

DESCRIPTION (provided by applicant): Synaptic mechanisms of inhibition represent some of the greatest gaps in our understanding of the processing of acoustic signals in the brainstem. The subtypes of neurons, with whom they interconnect, the efficacy of those connections, and how the size and shape of the inhibitory signals are controlled, all these remain unclear. Given the relation between inhibition as a target for drugs and disease in other brain regions it seems likely that a deep knowledge of inhibitory systems will be of clinical relevance for treating auditory disorders. In this proposal, we will address decisively each one of these points, focusing on the ubiquitous inhibitory neurotransmitter glycine. First, we will take advantage of the availability of lines of mice in which green fluorescent protein (GFP) is expressed in subsets of inhibitory cells to reveal the function and connectivity of common subtypes of auditory neurons that have been rarely studied using direct electrophysiological means. Second, we will identify mechanisms that control the duration of the inhibitory state, and focus on the role of transmitter clearance from the synaptic cleft and the promising role of GABA/glycine cotransmission in regulation of glycinergic decays. Finally, we will determine what mechanisms set whether glycine excites or inhibits postsynaptic neurons.

描述（由申请人提供）：突触抑制机制代表了我们对脑干中声信号处理的理解中的一些最大差距。神经元的亚型、它们与谁互连、这些连接的功效以及如何控制抑制信号的大小和形状，所有这些仍然不清楚。考虑到作为药物靶标的抑制与其他大脑区域疾病之间的关系，对抑制系统的深入了解似乎对治疗听觉障碍具有临床意义。在这项提案中，我们将果断地解决每一点，重点关注无处不在的抑制性神经递质甘氨酸。首先，我们将利用在抑制性细胞亚群中表达绿色荧光蛋白（GFP）的小鼠系来揭示听觉神经元常见亚型的功能和连接性，而这些神经元很少使用直接电生理学手段进行研究。其次，我们将确定控制抑制状态持续时间的机制，并重点关注突触间隙递质清除的作用以及 GABA/甘氨酸共传递在甘氨酸能衰变调节中的潜在作用。最后，我们将确定甘氨酸是兴奋还是抑制突触后神经元的机制。