Mechanisms of Dendrite Regeneration after Injury

损伤后树突再生的机制

基本信息

批准号：
9164083
负责人：
Katherine Louise Thompson-Peer
金额：
$ 9.84万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9164083
关键词：
Actins Affect Afferent Neurons Antibodies Axon Behavior Beryllium Biological Caenorhabditis elegans Calcium Calcium Signaling Caliber Cells Characteristics Cytoskeleton Defect Dendrite Regeneration Dendrites Dependence Detection Development Disease model Drosophila genus Electrophysiology (science)Embryo Exhibits Faculty Failure Genetic Goals Growth Injury Institution Ion Channel Knowledge Larva Learning Light Maintenance Membrane Potentials Mentors Microtubules Monitor Morphology Natural regeneration Nerve Degeneration Neurodegenerative Disorders Neuronal Injury Neurons Pattern Peripheral Nervous System Phase Play Process Pupa Reporter Research Role Sensory Signal Pathway Signal Transduction Staging Stimulus Stroke Synapses System Testing Touch sensation Training Transgenes Traumatic Brain Injury axon regeneration base career development cell type clinically relevant information processing injured juvenile animal mature animal member mutant neuron loss neuronal cell body neuronal circuitry optogenetics post-doctoral training prevent programs quantitative imaging receptive field research study response sensory stimulus skills tenure track tool trafficking transcription factor voltage

Actins Affect Afferent Neurons Antibodies Axon Behavior Beryllium Biological Caenorhabditis elegans Calcium Calcium Signaling Caliber Cells Characteristics Cytoskeleton Defect Dendrite Regeneration Dendrites Dependence Detection Development Disease model Drosophila genus Electrophysiology (science)Embryo Exhibits Faculty Failure Genetic Goals Growth Injury Institution Ion Channel Knowledge Larva Learning Light Maintenance Membrane Potentials Mentors Microtubules Monitor Morphology Natural regeneration Nerve Degeneration Neurodegenerative Disorders Neuronal Injury Neurons Pattern Peripheral Nervous System Phase Play Process Pupa Reporter Research Role Sensory Signal Pathway Signal Transduction Staging Stimulus Stroke Synapses System Testing Touch sensation Training Transgenes Traumatic Brain Injury axon regeneration base career development cell type clinically relevant information processing injured juvenile animal mature animal member mutant neuron loss neuronal cell body neuronal circuitry optogenetics post-doctoral training prevent programs quantitative imaging receptive field research study response sensory stimulus skills tenure track tool trafficking transcription factor voltage

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项目摘要

At the most straightforward level, a neuron receives information along dendrites, and sends information down an axon to synaptic contacts. Dendrites are injured by traumatic brain injury, stroke, and many forms of neurodegeneration, yet while factors that control axon regeneration after injury have been extensively studied, we know almost nothing about dendrite regeneration. My long term research goal is to understand the cellular mechanisms of dendrite regeneration after injury. During my graduate training with Dr Joshua Kaplan at Harvard, I used quantitative imaging, behavior, and C. elegans genetics to examine a key step in neuronal circuit development. For my postdoctoral training with Dr Yuh Nung Jan at UCSF, I have transitioned to studying the response to neurons to dendrite injury in Drosophila. I have found that the da sensory neurons in the Drosophila peripheral nervous system exhibit robust regeneration of dendrites after injury and am using this system to explore fundamental features of dendrite regeneration. I have observed that regenerated dendrites are identical to uninjured dendrites in many ways, like the trafficking of sensory ion channels and the expression of cell-type specific transcription factors. However the morphology and patterning of injury-induced dendrites are significantly defective compared to uninjured dendrites. Moreover, manipulations that alter the excitability of neurons specifically alter the regrowth of neurons after injury without affecting uninjured neurons, suggesting that dendrite regeneration is an activity-dependent process. I propose that developing a research program to deepen our knowledge about dendrite regeneration will create a new framework for understanding how neurons recover from injury. My short term research goals for the K99 mentored phase are to gain additional experimental skills to test the function of regenerated dendrites. These skills will facilitate the research proposed here: to investigate the activity dependence of dendrite regeneration; to examine the cell biological changes that underlie the alterations in regenerated dendrite morphology and their functional consequences; and explore the relationship between dendrite arbor maintenance and dendrite regeneration after injury. The proposed experimental training and the planned career development activities will prepare me to transition to leading an independent and productive research program as a tenure-track faculty member at a research institution.

在最直接的水平上，神经元沿树突接收信息，并将信息向下发送轴突以进行突触接触。树突受到创伤性脑损伤，中风和多种形式的神经变性的伤害，但是尽管对损伤后控制轴突再生的因素进行了广泛的研究，但我们几乎对树突再生一无所知。我的长期研究目标是了解损伤后树突再生的细胞机制。在哈佛大学的Joshua Kaplan博士的研究生培训期间，我使用定量成像，行为和秀丽隐杆线虫遗传学来检查神经元电路发育的关键步骤。对于我在UCSF的Yuh Nung Jan博士的博士后培训，我已经过渡到研究果蝇对果蝇损伤的神经元的反应。我发现果蝇周围神经系统中的DA感觉神经元在受伤后表现出强大的树突再生，并使用该系统探索树突再生的基本特征。我已经观察到，再生的树突在许多方面与未造成的树突相同，例如贩运感觉离子通道和细胞类型特异性转录因子的表达。但是，与未受伤的树突相比，损伤引起的树突的形态和模式显着有缺陷。此外，改变神经元的兴奋性的操纵特异性地改变了损伤后神经元的再生，而不会影响未受伤的神经元，这表明树突再生是一个依赖活性的过程。我建议制定一项研究计划来加深我们对树突再生的了解，将创建一个新的框架，以了解神经元如何从损伤中恢复。我对K99指导阶段的短期研究目标是获得其他实验技能，以测试再生树突的功能。这些技能将促进此处提出的研究：研究树突再生的活动依赖性；检查细胞生物学变化，这些变化是再生树突形态及其功能的改变的基础结果;并探索受伤后的树突植树维持和树突再生之间的关系。拟议的实验培训和计划中的职业发展活动将使我能够过渡到领导一项独立和生产性研究计划，成为研究机构的终身教师。