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: 10396539
• 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/10396539
• 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 circuit; neurodevelopment; neuronal cell body; novel; optical imaging; relating to nervous system; 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

总结 神经元编码各种各样的信号，每一种信号都与翻译感觉反应或感觉信号有特定的相关性。 记忆转化为行为细胞和突触是如何优化以满足这些需求的？我们的工作已经在 体外模型系统，以了解这种功能的专门化在树突的水平，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， 通过展示轴突起始段和神经末梢中的神经递质受体如何 在调节轴突和突触通讯中的独特作用。在这个建议中，我们将转向一个新的观点， 轴突的作用。除了它在尖峰信号单向传输中的功能外，我们还将研究亚阈值 在索马、轴突或终末中产生的信号沿着轴突以正向和反向传播 修改尖峰及其传播的方向。此外，我们还将研究钙如何释放 调节新生儿大脑兴奋机制。这些目标的关键将是使用精心挑选的 小鼠线，其特征在于用荧光团稀疏地标记神经元， 活脑切片中神经元的间隔，从树突到神经末梢。这项研究应该揭示 与动作电位平行运作的信号传导的新维度，特别是在神经元中， 神经微电路