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

概括 神经元编码各种信号，每个信号具有特定的相关性，用于翻译感官响应或 记忆成行为。细胞和突触如何优化以满足这些需求？我们的工作已经 体外模型系统，以了解树突水平上的功能专业，轴突初始 段和神经终端。实验室的研究扩大了神经元功能的经典观点 例如，通过显示轴突初始段和神经末端中的神经递质受体如何 修改轴突和突触通信的独特角色。在此提案中，我们将转向 轴突的作用。除了它在单向尖峰传输中的功能之外，我们还将研究子阈值 在躯体中产生的信号，轴突或端子沿着轴突向前和反向散布 修改尖峰及其传播的方向。此外，我们将研究钙如何释放 机制调节新生儿大脑的激发。这些目标的关键将是使用精心选择的 具有荧光团神经元稀疏荧光标记的小鼠系，清楚地揭示了每个神经元 从树突到神经末端的活脑切片中神经元的隔室。该研究应揭示 信号的新维度与动作电位并联，尤其是在中间神经元中 神经微电路