A transgenic songbird to image brain premotor sequence

转基因鸣禽对大脑前运动序列进行成像

基本信息

批准号：
9034727
负责人：
CARLOS LOIS
金额：
$ 26.53万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9034727
关键词：
Animal Model Animals Behavior Behavioral Biological Models Birds Brain Brain imaging Cell Nucleus Cells Clinical Complex Computers Data Development Disease Exhibits Generations Genetic Goals Head Image Individual Injection of therapeutic agent Injury Label Laboratories Lead Learning Mammals Maps Measurable Methods Modeling Monitor Motor Movement Movement Disorders Muscle Neurons Neurosciences Parkinson Disease Pathway interactions Pattern Prosthesis Reporter Resolution Sampling Science Sensory Signal Transduction Songbirds Stereotyped Behavior Stereotyping Stroke Synapsins System Techniques Training Transgenes Transgenic Animals Transgenic Organisms Ubiquitin C Variant Viral Viral Vector Virus brain machine interface cell type central nervous system injury effective therapy fluorescence microscope functional restoration improved insight learned behavior millisecond motor control motor deficit motor learning motor skill learning neuromechanism neuronal circuitry neuronal patterning next generation promoter public health relevance relating to nervous system response to injury sequence learning stereotypy tool zebra finch

项目摘要

DESCRIPTION (provided by applicant): The neural mechanisms underlying learned motor behaviors are one of the least understood aspects of neuroscience, yet treatment of motor deficits after injury or disease is a significant clinical need. A better understanding of the organization of motor control could lead to effective treatments that provide enhancements of motor plasticity, or brain machine interfaces for functional restoration. However, at the cellular level, little is known about how brain circuits are able to learn and reproduce temporal sequences. One the greatest challenges involved in investigating natural motor control is the lack of repeatability of the learned motor skill. To image neuronal activity during the execution o a highly complex, yet stereotyped, behavior we propose to develop a transgenic songbird expressing the genetically-encoded Ca++ indicator GCaMP6. We will use the zebra finch, a species that learns to produce an extremely stereotyped song pattern, with strikingly small trial-to trial variations. Thus, this system provides a rare model from which to tightly correlate functional changes in neuronal activity to specific and readily measurable behavioral changes. Uncovering principles relating motor behavior and cell type specific circuit activity will provide key insights governing sensory-motor learning, adaptive plasticity in response to injury, and also provide insights for the development of next generation brain-machine interfaces.

描述（由适用提供）：学习运动行为的基础神经元机制是神经科学的知识最低的方面之一，但是受伤或疾病后运动缺陷的治疗是临床上的巨大需求。更好地了解运动控制的组织可能会导致有效的治疗方法，从而增强运动可塑性或用于功能恢复的脑机界面。但是，在细胞水平上，关于脑电路如何能够学习和繁殖临时序列知之甚少。研究自然运动控制涉及的最大挑战之一是学习的运动技能缺乏可重复性。为了在执行过程中成像神经元活动，我们提出了一种高度复杂但刻板印象的行为，我们建议开发一种表达一般编码的Ca ++指示器GCAMP6的转基因鸣鸟。我们将使用斑马罚款，该物种学会产生极为刻板的歌曲模式，并具有巨大的试验对试验变化。该系统提供了一个罕见的模型，从中，将神经元活动的功能变化紧密相关，与特定且易于测量的行为变化。揭示有关运动行为和细胞类型特异性电路活动的原则将提供有关感官运动学习，自适应可塑性的关键见解，并为造成伤害的响应提供了见解，以开发下一代脑机界面。