A novel neuroimaging approach to mapping the neural circuits underlying behavior

一种新的神经影像方法来绘制行为背后的神经回路

基本信息

批准号：
7620020
负责人：
Shawn Xu
金额：
$ 30.9万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-05 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7620020
关键词：
Afferent Neurons American Society of Hematology Animal Model Animals Behavior Behavior Control Behavioral Biological Models Bipolar Disorder Caenorhabditis elegans Calcium Chemicals Cloning Defect Development Drosophila genus Epilepsy Exhibits Genes Genetic Genetic Models Homologous Gene Human Image Interneurons Lasers Lead Locomotion Mammals Maps Mediating Microsurgery Modeling Molecular Genetics Movement Disorders Names Nematoda Nervous system structure Neurobiology Neuromuscular Junction Neurons Nose Optics Organism Osmotic Shocks Output Pattern Phylogeny Play Process Research Resolution Role Sensory Stimulus System Technology Thinness Time Touch sensation Work avoidance behavior behavior test fly genetic manipulation human disease insight interest nervous system disorder neural circuit neuroimaging neuromechanism novel prevent ratiometric relating to nervous system response tool

项目摘要

DESCRIPTION (provided by applicant): Neural circuits are the functional and structural units of the nervous system. Defects in neural circuit function and development lead to a variety of neurological disorders. We are interested in understanding how information is processed by neural circuits and how genes regulate such processing, and how this ultimately produces and reshapes behavioral output. As numerous neural mechanisms are found to be conserved across phylogeny, genetic model organisms, such as C. elegans and Drosophila, have been widely utilized to study various phenomena in neurobiology. About two-third of human disease genes have homologs in these organisms. However, certain technological shortfalls have greatly hampered the use of these genetic organisms as a model for neurobiology research. In particular, there is no technology available that allows one to record neural activity in behaving worms or flies. Consequently, all current studies have been limited to recording neural activity in immobilized or semi-immobilized, but not in freely-behaving animals, making it difficult to reliably correlate neural activity and behavior. Here we have, for the first time, developed a novel noninvasive neuroimaging system that can record neuronal activity in freely-behaving worms at single neuron resolution, thus allowing for mapping the neural circuits underlying behavior. In the current proposal, by taking advantage of this novel neuroimaging system in conjunction with laser microsurgery and molecular genetic tools, we will define the neural circuits underlying some classic worm behaviors. In addition, we will further develop the system by introducing more advanced functionalities. The proposed work will provide novel insights into how the nervous system and genes control behavior in mammals. Many types of neurological disorders (e.g., epilepsy, movement disorders and bipolar disorder) are manifested by behavioral abnormalities that result from defective neural circuit function and development. Our work will provide novel insights into how neural circuits and genes control normal behavior and how defects in this process lead to those neurological disorders.

描述（由申请人提供）：神经回路是神经系统的功能和结构单位。神经回路功能和发育的缺陷导致多种神经系统疾病。我们有兴趣了解神经回路如何处理信息，以及基因如何调节此类处理，以及最终如何产生和重塑行为输出。由于发现许多神经机制在系统发育中是保守的，因此遗传模型生物（例如秀丽隐杆线虫和果蝇）已被广泛用于研究神经生物学中的各种现象。大约三分之二的人类疾病基因在这些生物中具有同源物。但是，某些技术短缺极大地阻碍了这些遗传生物作为神经生物学研究模型的使用。特别是，没有可用的技术可以记录在蠕虫或果蝇中的神经活动。因此，当前的所有研究都仅限于记录固定或半肌动物的神经活动，但在自由行为的动物中不仅限于可靠地相关的神经活动和行为。在这里，我们首次开发了一种新型的无创神经成像系统，该系统可以记录在单个神经元分辨率下自由地行为的蠕虫中的神经元活性，从而允许映射基本行为的神经回路。在当前的建议中，通过利用这种新型的神经影像系统与激光微型手术和分子遗传工具，我们将定义一些经典蠕虫行为的神经回路。此外，我们将通过引入更高级的功能进一步开发系统。拟议的工作将提供有关神经系统和基因如何控制哺乳动物行为的新见解。许多类型的神经系统疾病（例如癫痫，运动障碍和躁郁症）由受缺陷的神经回路功能和发育导致的行为异常表现出来。我们的工作将提供有关神经回路和基因如何控制正常行为以及该过程中缺陷如何导致这些神经系统疾病的新颖见解。