Elucidating mechanisms of active dendritic integration in vivo

神经电路通过过滤、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制。这个项目的重点是揭开 使用电生理学、双光子成像和光遗传学的这些过程的基础。钥匙 目的是了解神经元树突在体内电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的电刺，这可能提供了一个关键的方面 到细胞层面的信息处理。这样一个活跃的机制是如何运作和发挥作用的 在一种行为动物中扮演的角色尚不清楚。通过从细小的远端直接记录细胞内电活动 体内感觉加工过程中的树突及其母细胞胞体，以及钙离子的双光子成像 在突触输入和树突的动力学方面，我们试图了解活跃的树突机制是如何起作用的 到突触整合，以及它们的调节如何影响感觉整合。在这项研究中，我们将解决 在活体内存在以下问题：1)树突突触输入和树突尖峰之间的关系是什么？ 2)树突棘在触发轴突动作电位方面有多有效；3)树突棘的功能作用是什么？ 树突棘波在塑造神经元输出的感受野特性中的作用。该项目的发现将既 进一步加深我们对细胞信息处理的基本机制的理解，并提供 以此为立足点破译阿尔茨海默病和其他疾病中神经回路是如何受到影响的 神经生理学障碍。

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.