Development and Function of Central Neuron Dendrites

中枢神经元树突是惊人复杂的三维结构，形成神经元的隔室，用于接收突触输入。因此，树突结构影响大脑功能的两个基本方面：首先，它决定了哪些突触前神经元可以接触突触后树突乔木，从而影响神经回路的开发和设计。其次，它影响突触后信号的总和和计算。因此，健康的脑功能依赖于正确的树突结构发育，而树突缺陷是许多神经系统疾病的病理生理学标志。因此，识别树突结构发育和树突状乔木上突触放置的分子机制对于理解健康和患病大脑中的神经回路发育和功能至关重要。该项目将联合收割机遗传工具与果蝇遗传模型系统中的树突结构定量分析以及光生理和电生理记录相结合，以揭示树突采取正确完形的分子机制，特别关注树突自我回避和中枢神经元间距的潜在机制（目标1）。 在下一步中，我们将解决局部突触活动和自我回避的相互作用，以正确的树突结构的发展（目标2）。由于我们最近发现了细胞识别分子Dscam 1在促进树突生长和分支方面的一种新的和意想不到的功能，我们现在将讨论潜在的分子机制（目的3）。在这些发育研究的基础上，我们将操纵具有明显不同功能的不同类型神经元中的树突结构，并采用电生理学和光生理学方法以及行为测试来测试树突缺陷导致的功能后果（目的4）。因此，我们期待新的见解，树突状结构的发展和不同的树突状结构功能的神经元功能的具体作用的调节。

Central neuron dendrites are stunningly complex three-dimensional structures and form the compartment of a neuron for receiving synaptic input. Consequently, dendritic architecture affects two fundamental aspects of brain function: First, it dictates which presynaptic neurons can contact the postsynaptic dendritic arbor, thus impacting neural circuit development and design. Second, it affects the summation and computation of postsynaptic signals. Consequently, healthy brain function relies on correct dendritic structure development, and dendritic defects are pathophysiological hallmarks of numerous neurological diseases. Therefore, identifying the molecular mechanisms underlying dendritic architecture development and synapse placement on dendritic arbors is imperative to understanding neural circuit development and function in the healthy and in the diseased brain. This project will combine genetic tools with quantitative dendritic structure analysis and opto- and electrophysiological recordings in the Drosophila genetic model system to unravel molecular mechanisms by which dendrites take on their correct gestalt, with specific focus on the mechanisms underlying dendritic self-avoidance and spacing of central neurons (aim 1). In the next step we will address the interplay of local synaptic activity and self-avoidance for correct dendritic architecture development (aim 2). Since we have recently uncovered a novel and unexpected function of the cell recognition molecule, Dscam1, in promoting dendrite growth and branching, we will now address the underlying molecular mechanisms (aim 3). Building on these developmental studies, we will then manipulate dendritic structure in different types of neurons with distinctly different functions and employ electro- and optophysiological approaches as well as behavioral testing to test the functional consequences that result from dendritic defects (aim 4). Therefore, we expect novel insight into the regulation of dendritic structure development and into the specific roles of distinct dendritic architecture features for neuronal function.