Elucidating mechanisms of active dendritic integration in vivo

阐明体内主动树突整合的机制

• 批准号: 10621807
• 负责人: Ikuko Smith
• 金额: $ 36.6万
• 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/10621807
• 关键词: Acceleration; 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; Maps; 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; efficacy evaluation; 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.

神经电路通过过滤、放大和集成电信号来处理细胞水平的信息 由突触输入和电压门控机制产生和调节。 使用电生理学、双光子成像和光遗传学来支持此类过程的基础。 目的是了解神经树突在体内电路活动期间处理信息中的作用。 树突可以像轴突一样发射再生电尖峰，这可能提供一个关键方面 细胞水平的信息处理如何参与并发挥作用。 通过直接记录精细远端的细胞内电活动，其在行为动物中的作用仍不清楚。 体内感觉处理过程中的树突及其母体，以及钙的双光子成像 突触输入和树突的动力学，我们试图了解活跃的树突机制如何做出贡献 突触整合，以及它们的调节如何影响感觉整合。 体内以下问题：1）树突突触输入和树突尖峰之间的关系是什么， 2) 树突尖峰在触发轴突动作电位方面有多有效，以及 3) 树突尖峰的功能作用是什么 该项目的发现将在塑造神经输出的感受野特性方面发挥树突尖峰的作用。 进一步加深我们对细胞信息处理基本机制的理解，并提供 破译神经回路在阿尔茨海默病和其他疾病中如何受到影响的立足点 神经生理障碍。