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

总结