Elucidating mechanisms of active dendritic integration in vivo

阐明体内主动树突整合的机制

• 批准号: 10504968
• 负责人: Ikuko Smith
• 金额: $ 36.69万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10504968
• 关键词: Action Potentials; Address; Affect; Alzheimer' s Disease; Animals; Axon; Brain; Calcium; Code; Coupled; Data; Dendrites; Dendritic Spines; Disease; Distal; Electrophysiology (science); Event; Exhibits; Fire - disasters; Frequencies; Functional disorder; Generations; Image; In Vitro; Individual; Injections; Knowledge; Lead; Location; Measurement; Mus; Nature; Neurons; Output; Parents; Play; Process; Property; Reporting; Role; Sensory; Signal Transduction; Site; Sodium; Somatostatin; Spatial Distribution; Synapses; Techniques; Testing; Vertebral column; Visual Cortex; Whole-Cell Recordings; awake; calcium indicator; flexibility; hippocampal pyramidal neuron; in vivo; information processing; inhibitory neuron; insight; nervous system disorder; neural circuit; neuronal cell body; neurophysiology; neurotrophic factor; optogenetics; patch clamp; postsynaptic; receptive field; regenerative; response; sensory integration; signal processing; two-photon; voltage

Neural circuitry processes information at the cellular level by filtering, amplifying, and integrating electrical signals generated and modulated by synaptic input and voltage-gated mechanisms. This project focuses on uncovering the underpinnings of such processes using electrophysiology, two-photon imaging, and optogenetics. The key aim is to understand the role of neuronal dendrites in processing information during in vivo circuit activity. Dendrites can fire regenerative electrical spikes much like axons, and this potentially provides a critical aspect to information processing at the cellular level. How such an active mechanism is engaged and plays a functional role in a behaving animal remains unclear. By directly recording intracellular electrical activity from fine distal dendrites and their parent somas during sensory processing in vivo, along with two-photon imaging of calcium dynamics at synaptic inputs and dendrites, we seek to understand how active dendritic mechanisms contribute to synaptic integration, and how their modulation affects sensory integration. In this study, we will address the following questions in vivo: 1) What is the relationship between dendritic synaptic inputs and dendritic spiking, 2) how effective are dendritic spikes in triggering axonal action potentials, and 3) what is the functional role of dendritic spikes in sculpting the receptive field properties of neuronal output. Findings from the project will both further our understanding of the fundamental mechanisms of cellular information processing and provide a foothold to decipher how neural circuitry is affected in conditions such as Alzheimer’s Disease and other neurophysiological disorders.

神经回路通过过滤、放大和整合电信号在细胞水平上处理信息 由突触输入和电压门控机制产生和调节。这个项目的重点是发现 使用电生理学、双光子成像和光遗传学的这些过程的基础。关键 目的是了解神经元树突在体内回路活动过程中处理信息的作用。 树突可以像轴突一样发射再生电尖峰，这可能提供了一个关键方面， 到细胞水平的信息处理。这样一个积极的机制是如何参与和发挥作用的， 在动物行为中的作用尚不清楚。通过直接记录细胞内电活动， 树突和它们的母体胞体在体内感觉加工过程中，沿着钙离子的双光子成像 动态突触输入和树突，我们试图了解如何积极的树突机制有助于 突触整合，以及它们的调节如何影响感觉整合。在本研究中，我们将讨论 以下问题在体内：1）树突突触输入和树突尖峰之间的关系是什么， 2)树突棘波在触发轴突动作电位方面有多有效，以及3） 树突尖峰在塑造神经元输出的感受野特性中的作用。该项目的结果将 进一步了解细胞信息处理的基本机制， 立足点，以破译神经回路是如何影响的条件，如阿尔茨海默氏症和其他 神经生理紊乱