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Heterologous expression of an invertebrate sodium channel for neuronal activation

用于神经元激活的无脊椎动物钠通道的异源表达

基本信息

批准号：
7842509
负责人：
ADAM RORY MCQUISTON
金额：
$ 18.69万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7842509
关键词：
Affect Agonist Anesthetics Antiepileptic Agents Anxiety Bathing Biological Neural Networks Brain Central Nervous System Agents Central Nervous System Diseases Chemicals Development Disease Electric Stimulation Electrodes Epilepsy Ethanol FMRFamide Functional disorder Gene Proteins Genes Glutamates Hippocampus (Brain)Individual Interneurons Invertebrates Investigation Ligands Link Memory Mental disorders Methods Modeling Nerve Tissue Nervous System Physiology Nervous system structure Neuraxis Neurologic Neurons Neurotransmitters Peptides Perfusion Population Preparation Process Proteins Role Schizophrenia Site Slice Snails Sodium Channel Spasm Synapses System Techniques Ultraviolet Rays base cell type drug development hypnotic improved information processing method development millisecond nervous system disorder photolysis postsynaptic pressure promoter protein expression public health relevance receptor relating to nervous system sedative tool tool development

项目摘要

DESCRIPTION (provided by applicant): Understanding how individual neuronal subtypes contribute to neural network function is vital to understanding how the nervous system functions and in understanding how dysfunction of specific neuronal subtypes contributes to neurological and psychiatric diseases. However, current methods used to activate neurons or neuronal processes in intact nervous tissue have not permitted the indiscriminate excitation of an individual subtype of neuron. This proposal plans to develop a technique that will permit the selective activation of individual subtypes of neurons by expressing in specific types of neurons genes of proteins that are capable of depolarizing only those neurons when the activator protein is stimulated. The activator protein we will use is the snail FMRFamide ligand-gated sodium channel (FaNaC). FaNaC is ideal because it is not found in the mammalian nervous system thereby allowing selective activation of only the neurons in which it has been expressed. To improve this technique, we will attempt to synthesize a light-sensitive compound that can activate FaNaC expressing neurons with millisecond precision. Furthermore, we will use rapid activation of FaNaC or other heterologously-expressed proteins to study how specific types of inhibitory interneurons in hippocampal CA1 are controlled by specific types of surrounding neurons. Because inhibitory interneurons have roles in CNS diseases such as epilepsy, anxiety, schizophrenia and spasm, information obtained from these studies will be relevant to understanding how inhibitory interneuron dysfunction may contribute to abnormal CNS function. PUBLIC HEALTH RELEVANCE: This study proposes to develop a gene based tool that will permit the activation of specific types of neurons in intact nervous tissue. We plan to use this tool to examine the function of inhibitory interneurons in controlling hippocampal network activity. These studies will provide us with a model to understand the role of specific neurons in normal brain function and in psychiatric and neurological disorders.

描述（由申请人提供）：了解单个神经元亚型如何促进神经网络功能对于了解神经系统如何发挥功能以及了解特定神经元亚型的功能障碍如何促进神经和精神疾病至关重要。然而，目前用于激活完整神经组织中的神经元或神经元过程的方法不允许不加选择地激发单个亚型的神经元。该提案计划开发一种技术，该技术将允许通过在特定类型的神经元中表达蛋白质的基因来选择性激活神经元的个体亚型，当激活蛋白被刺激时，该蛋白质能够仅使那些神经元去极化。我们将使用的激活蛋白是蜗牛FMRFamide配体门控钠通道（FaNaC）。FaNaC是理想的，因为它在哺乳动物神经系统中没有发现，从而仅允许选择性激活其中表达它的神经元。为了改进这项技术，我们将尝试合成一种光敏化合物，它可以以毫秒级的精度激活表达FaNaC的神经元。此外，我们将使用快速激活FaNaC或其他异源表达的蛋白质来研究海马CA1中特定类型的抑制性中间神经元如何由特定类型的周围神经元控制。由于抑制性中间神经元在CNS疾病如癫痫、焦虑、精神分裂症和痉挛中起作用，因此从这些研究中获得的信息将有助于理解抑制性中间神经元功能障碍如何导致CNS功能异常。公共卫生关系：这项研究提出开发一种基于基因的工具，允许激活完整神经组织中特定类型的神经元。我们计划使用这个工具来检查抑制性中间神经元在控制海马网络活动中的功能。这些研究将为我们提供一个模型，以了解特定神经元在正常脑功能以及精神和神经系统疾病中的作用。