Regulation of axonal and synaptic signaling in interneurons

中间神经元轴突和突触信号传导的调节

• 批准号: 10608087
• 负责人: LAURENCE O TRUSSELL
• 金额: $ 52.38万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608087
• 关键词: Action Potentials; Axon; Behavior; Biological Models; Brain; Calcium; Cells; Communication; Dendrites; Dimensions; Electrophysiology (science); Interneurons; Label; Memory; Mus; Nerve; Neuromodulator; Neurons; Neurotransmitter Receptor; Pharmacologic Substance; Regulation; Research; Role; Sensory; Signal Transduction; Slice; Stretching; Synapses; Translating; Work; brain tissue; fluorophore; imaging modality; in vitro Model; neonatal brain; neural; neural circuit; neurodevelopment; neuronal cell body; novel; optical imaging; response; transmission process

Summary Neurons encode a wide variety of signals, each with specific relevance for translating a sensory response or memory into behavior. How are cells and synapses optimized to meet these needs? Our work has used in vitro model systems to understand such specializations of function at the level of the dendrite, the axon initial segment and the nerve terminal. The lab's studies have stretched the classical views of neuronal function, for example by showing how neurotransmitter receptors in the axon initial segment and in the nerve terminal have unique roles for modifying axon and synaptic communication. In this proposal, we will turn to a new view of the role of the axon. Beyond its function in the one-way transmission of spikes, we will examine how subthreshold signals generated in the soma, the axon or the terminal spread along the axon in the forward and reverse directions to modify the spike and its propagation. Additionally, we will examine how calcium release mechanism modulate excitation in neonatal brain. Key to these aims will be the use of carefully selected mouse lines that feature sparse fluorescent labeling of neurons with fluorophores that clearly reveal each compartment of the neuron in living brain slices, from dendrite to nerve terminal. The research should reveal new dimensions of signaling that operate in parallel with the action potential, particularly in interneurons in neural microcircuits

概括 神经元编码各种各样的信号，每个信号都与翻译感官反应或 记忆转化为行为。如何优化细胞和突触以满足这些需求？我们的工作已用于 体外模型系统来理解树突水平上的这种功能特化，轴突初始 段和神经末梢。该实验室的研究扩展了神经元功能的经典观点， 举例说明轴突起始段和神经末梢中的神经递质受体如何 改变轴突和突触通讯的独特作用。在本提案中，我们将转向一个新的观点： 轴突的作用。除了其单向传输尖峰的功能之外，我们还将研究亚阈值如何 体细胞、轴突或末梢产生的信号沿轴突正向和反向传播 修改尖峰及其传播的方向。此外，我们将检查钙如何释放 机制调节新生儿大脑的兴奋。这些目标的关键是使用精心挑选的 具有神经元稀疏荧光标记的小鼠品系，荧光团可以清楚地显示每个神经元 活体脑切片中的神经元区室，从树突到神经末梢。研究应该揭示 信号传导的新维度与动作电位并行运作，特别是在中间神经元中 神经微电路