Mechanisms and functions of Drosophila motoneuron dendritic shape development

果蝇运动神经元树突形状发育的机制和功能

基本信息

批准号：
8874766
负责人：
STUART J NEWFELD
金额：
$ 22.54万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8874766
关键词：
Adult Affect Afferent Neurons Animals Architecture Behavior Biological Models Brain Calcium Cells Complex Cues Cyclic AMP-Dependent Protein Kinases Databases Defect Dendrites Development Disease Drosophila genus Ensure Fragile X Syndrome Genetic Genetic Models Growth Human Image Individual Knowledge Length Life Mechanoreceptors Mediating Modeling Molecular Morphology Motor Neurons Nature Nerve Degeneration Neuraxis Neurodegenerative Disorders Neurons Neuropil Pattern Phenotype Process Records Controls Regulation Role Shapes Signal Pathway Signal Transduction Staging Structure Synapses System Test Result Testing Trees base cell type cellular imaging fly genetic manipulation information processing insight neural circuit neuron development novel patch clamp postsynaptic postsynaptic neurons presynaptic presynaptic neurons research study response success synaptogenesis tool

项目摘要

DESCRIPTION (provided by applicant): The brains of all animals are composed out of individual neurons with cell type specific morphologies. The remarkably diverse dendritic architecture of neurons determines two fundamental aspects of neural circuitry: First, it dictates which presynaptic neurons can contact the postsynaptic dendritic arbor. Second, it affects the summation and computation of synaptic input in the postsynaptic dendritic arbor. Consequently, healthy brain function relies on the correct development of dendritic structure, and dendritic architecture defects have been associated with a number of neurodegenerative diseases, such as Rett- and Fragile-X Syndrome. Identifying the molecular mechanisms that regulate dendritic architecture development and synapse placement on dendritic arbors is imperative to understanding neural circuit development in the healthy and in the diseased brain. Despite recent success in identifying key molecular mechanisms regulating dendritic arbor development, our knowledge on the functional consequences of dendritic architecture mis-regulation for synaptic partner matching and for synaptic input processing in the postsynaptic neuron remains fragmentary. This study aims to unravel molecular mechanisms underlying specific aspects of dendritic architecture development as well as the functional consequences of false regulation. During development dendritic structure is regulated by innate genetic factors, guidance cues, humoral cues, and by neuronal activity. Although some of these signals may be integrated by similar intracellular signaling pathways, different signals can independently affect various dendritic features in the same neuron, such as dendritic branch lengths and numbers, dendritic territory borders, and the correct spacing of dendritic arbors within their territories. During recent years, fundamental new insights into the molecular mechanisms that control dendritic self-avoidance and tiling, and thereby correct dendritic arbor spacing, have come from the Drosophila genetic model system. However, it remains largely unclear how these mechanisms interact with synaptic partner matching during circuit assembly in the central nervous system. Therefore, the proposed experiments will test how dendritic self-avoidance mechanisms interact with central synapse formation during dendritic arbor development of Drosophila motoneurons. A quantitative database on control motoneuron dendritic architecture features will serve as bedrock for testing the roles of key molecules mediating dendritic repulsion by targeted genetic manipulation. In addition, we have identified sensory neurons that synapse onto these motoneurons, allowing one to test for functional interactions between dendritic repulsion and synaptic partner matching during dendritic arbor growth. Furthermore, correct and false dendritic architecture regulation will be related to neuronal function by computational approaches and electrophysiological recordings in control and genetically manipulated animals. We expect to gain novel insight into the regulation of dendritic arbor architecture during development as well as into the functional consequences of dendritic arbor defects in mature neurons.

描述（由申请人提供）：所有动物的大脑都是由具有细胞类型特异性形态的单个神经元组成的。神经元的千差万别的树突状建筑决定了神经回路的两个基本方面：首先，它决定了哪些突触前神经元可以与突触后的树突状植物园联系。其次，它会影响突触后树突状植物的突触输入的求和和计算。因此，健康的大脑功能依赖于树突结构的正确发展，而树突状结构缺陷已与许多神经退行性疾病（例如RETT和脆弱的X综合征）相关。确定在树突状乔木上调节树突状结构发展和突触位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至关重要。尽管最近在确定调节树突状乔木发育的关键分子机制方面取得了成功，但我们对树突状结构的功能后果的知识，对突触伴侣匹配和突触后神经元中的突触输入处理的功能后果仍然存在。这项研究旨在阐明树突状建筑发展特定方面的基础分子机制以及错误调节的功能后果。在开发过程中，树突结构受先天遗传因素，指导线索，体液提示和神经元活性的调节。尽管这些信号中的一些可以通过相似的细胞内信号通路进行集成，但是不同的信号可以独立地影响同一神经元中的各种树突特征，例如树突状分支长度和数字，树突状区域边界以及在其领土内的树突阶层的正确间距。近年来，对控制树突状自我避免和平铺的分子机制的基本新见解，从而正确的树突植物间距来自果蝇遗传模型系统。但是，在很大程度上不清楚这些机制如何与中枢神经系统电路组装过程中的突触伴侣匹配相互作用。因此，提出的实验将测试树突状自我避免机制如何与果蝇运动神经元的树突状乔木发育过程中中央突触形成相互作用。关于控制运动神经元树突状结构特征的定量数据库将用作基岩，以测试通过靶向基因操作介导树突状排斥的关键分子的作用。此外，我们已经确定了在这些运动神经元上突触的感觉神经元，从而可以测试树突状抑制和突触伴侣在树突状植物植物生长过程中的功能相互作用。此外，正确与错误的树突状结构调节将通过对照和遗传操纵动物中的计算方法和电生理记录与神经元功能有关。我们希望在开发过程中对树突状乔木建筑的调节以及对成熟神经元中树突状乔木缺陷的功能后果的调节进行新颖的见解。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Preparation of Drosophila central neurons for in situ patch clamping.

用于原位膜片钳的果蝇中枢神经元的制备。

DOI：
10.3791/4264
发表时间：
2012
期刊：
Journal of visualized experiments : JoVE
影响因子：
0
作者：
Ryglewski,Stefanie;Duch,Carsten
通讯作者：
Duch,Carsten

Transient BK outward current enhances motoneurone firing rates during Drosophila larval locomotion

DOI：
10.1113/jp271323
发表时间：
2015-11-15
期刊：
JOURNAL OF PHYSIOLOGY-LONDON
影响因子：
5.5
作者：
Kadas, Dimitrios;Ryglewski, Stefanie;Duch, Carsten
通讯作者：
Duch, Carsten

Tiling among stereotyped dendritic branches in an identified Drosophila motoneuron.

DOI：
10.1002/cne.22380
发表时间：
2010-06-15
期刊：
JOURNAL OF COMPARATIVE NEUROLOGY
影响因子：
2.5
作者：
Vonhoff, F.;Duch, C.
通讯作者：
Duch, C.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior

DOI：
10.1073/pnas.1416247111
发表时间：
2014-12-16
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Ryglewski, Stefanie;Kadas, Dimitrios;Duch, Carsten
通讯作者：
Duch, Carsten

Drosophila as a model for MECP2 gain of function in neurons.

果蝇作为 MECP2 在神经元中获得功能的模型。