Basal Ganglia-Thalamic Interactions in Behaving Songbirds During Learning

鸣禽学习过程中基底神经节-丘脑的相互作用

基本信息

批准号：
8711569
负责人：
Jesse Heymann Goldberg
金额：
$ 24.81万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8711569
关键词：
Address Animals Auditory Axon Basal Ganglia Basal Ganglia Diseases Behavior Behavior Control Benchmarking Biological Models Biology Birds Brain Cell Nucleus Cell physiology Cells Code Cognitive Science Complex Corpus striatum structure Development Devices Digital Signal Processing Disease Doctor of Philosophy Dystonia Electrodes Exhibits Faculty Fees Funding Goals Grant Hour Human Huntington Disease Image Implant Institutes Laboratories Learning Mammals Mentors Methods Modeling Motor Motor Cortex Motor Skills Movement Neurons Operant Conditioning Output Paper Parkinson Disease Pathway interactions Patient Care Patients Pattern Performance Phase Play Population Positioning Attribute Postdoctoral Fellow Presynaptic Terminals Process Research Research Training Role Series Signal Transduction Songbirds Structure Synapses Techniques Technology Testing Thalamic structure TimeLine Training Training Support Translating Vertebrates Work Writing auditory feedback behavior influence career cell type clinically relevant conditioning control trial design extracellular falls ganglion cell graduate student human disease in vivo insight medical schools motor control motor learning nervous system disorder neuropsychiatry novel post-doctoral training postsynaptic programs public health relevance relating to nervous system research study sequence learning skills two-photon vocal learning

项目摘要

DESCRIPTION (provided by applicant): The basal ganglia (BG) circuit is a clinically relevant group of deep brain structures that appear to play similar functions in humans and birds-motor sequence learning. Even though current therapies in humans involve the stimulation of electrodes chronically implanted into BG structures, we still do not understand how electrical signals propagate through the circuit to influence behavior. Songbirds have specialized BG pathway devoted entirely to single task-song learning. Having performed the first recordings from distinct cell classes in the songbird BG (Goldberg and Fee, 2010; Goldberg et al., 2010), I am now poised to ask basic questions of BG function: How are BG outputs processed in the thalamus? How do distinct BG cell classes implement motor learning? What are the neural interactions within the BG circuit? In this proposal, I outline the path to my long term goal: to build a laboratory that harnesses the advantages of the songbird model system to study how basal ganglia microcircuits contribute to normal and abnormal motor function. For my PhD thesis, I used cellular physiology and two-photon imaging to study distinct cell classes in the cortical microcircuit. In medical school, I was trained in the care of patients with basal ganglia-related neurological disease, and in the first phase of my post-doctoral training, I have learned to record from connected neurons in the basal ganglia of freely moving animals. The training plan formulated in this proposal is specifically designed to bring me new techniques that will enable me to execute novel experiments and to transition to an independent position. For example, my immediate goals are to learn the computational, digital signal processing skills required to implement a novel song-conditioning paradigm, to develop a new method for extracellular recording from multiple neurons simultaneously during behavior, and to learn to use a recently developed intracellular microdrive for recording intracellularly from freely moving animals. These goals are to be completed in the mentored phase, before I apply for positions in the fall of 2011. As I acquire these techniques, I will be able to address basic questions of basal ganglia and thalamic function. First, I will examine how the motor thalamus integrates its two major inputs, from the BG and the cortex, by recording from connected pallidal and thalamic neurons, and by recording from antidromically identified corticothalamic projection neurons during singing. Next, I will examine BG output signals during experimentally controlled motor learning by combining neural recordings with a novel conditional auditory feedback paradigm that induces rapid trial and error song learning. Finally, I will embark on a long-term project of studying how each of the six major BG cell classes changes its activity during this learning, and how small groups of these neurons interact during behavior. This final aim includes the development of a technique to record intracellularly from BG neurons in singing birds, and constitutes the research program that I will continue, with Michale Fee's support, in the R00 phase of this grant. This training and research will take place in Michale Fee's laboratory at the McGovern Institute for Brain and Cognitive Sciences at MIT, where I am surrounded by talented graduate students, post-docs and faculty. The department is very stimulating with two weekly seminar series, world-renowned speakers and first rate facilities. Finally, even though Michale is well funded (two R01s), I am one of only two post-docs in the lab. This means Michale and I are very invested in one another and we frequently spend hours per day together, discussing experiments, writing papers and building new devices. As part of this grant resubmission Michale and I carefully formulated the experiments, the training plan, and the path to independence, and he has agreed to personally train and support me as I transition to the R00 phase, when I will begin to pursue the role that specific striatal and pallidal cell classes play in BG function. The timeline for these endeavors, which will constitute my benchmarks for progress, is presented in the Career Goals section of this proposal.

描述（由申请人提供）：基底神经节（BG）电路是一组临床上相关的深脑结构，在人类和鸟类运动序列学习中似乎起着相似的功能。即使当前人类中的疗法涉及刺激慢性植入BG结构的电极，但我们仍然不了解电信号如何通过电路传播以影响行为。 Songbirds拥有专门的BG途径，完全专门用于单个任务歌曲学习。在Songbird BG中的不同细胞类中执行了第一批录音（Goldberg and Fee，2010； Goldberg等，2010），我现在准备问BG功能的基本问题：thalamus中如何处理BG输出？不同的BG细胞类别如何实施运动学习？ BG电路中的神经相互作用是什么？在此提案中，我概述了我长期目标的道路：建立一个利用鸣鸟模型系统优势的实验室，以研究基底神经节微电路如何促进正常和异常的运动功能。对于我的博士学位论文，我使用细胞生理学和两光子成像来研究皮质微电路中不同的细胞类别。在医学院，我接受了基础神经节相关神经系统疾病的患者的护理，在我的博士后培训的第一阶段，我学会了从自由移动动物的基底神经节中的连接神经元中记录的记录。该提案中制定的培训计划是专门设计的，旨在为我带来新的技术，使我能够执行新颖的实验并过渡到独立的位置。例如，我的近期目标是学习实施新颖的歌曲调节范式所需的计算，数字信号处理技能，以在行为期间同时从多个神经元中开发出一种新的细胞外录制方法，并学会使用最近开发的细胞内的细胞内。微型训练可从自由移动的动物记录细胞内。这些目标将在我在2011年秋季申请职位之前在指导阶段完成。当我获得这些技术时，我将能够解决基底神经节和丘脑功能的基本问题。首先，我将通过记录连接的苍白球和丘脑神经元的记录，以及从唱片中录制的，在唱歌过程中记录了电动机丘脑的两个主要输入，即BG和皮层的两个主要输入。接下来，我将通过将神经记录与一种新型有条件的听觉反馈范式相结合，从而在实验控制的运动学习过程中检查BG输出信号，从而引起快速试验和错误的歌曲学习。最后，我将启动一个长期的项目，以研究六个主要的BG细胞类别中的每一个如何改变其在学习过程中的活性，以及这些神经元的小组在行为过程中如何相互作用。这个最终目的包括开发一种技术，以唱歌鸟类中的BG神经元的细胞内记录，并构成该研究计划，我将在米歇尔·费（Michale Fee）的支持下继续在这笔赠款的R00阶段。这项培训和研究将在MIT麦戈文大脑和认知科学研究所的Michale Fee的实验室进行，在那里我被才华横溢的研究生，毕业后和教职员工所包围。该部门非常激发两个每周的研讨会系列，世界知名的演讲者和一流的设施。最后，即使Michale资助良好（两个R01），我还是实验室中仅有的两个邮政事故之一。这意味着Michale和我相互投入，我们经常一起度过几个小时，讨论实验，撰写论文并构建新设备。作为这项赠款重新提交的一部分，我和我仔细制定了实验，培训计划和独立途径，当我将开始担任该职位时，他同意亲自培训和支持我该特定的纹状体和颗粒细胞类在BG功能中发挥作用。这些努力的时间表将构成我的进步基准，在本提案的职业目标部分中提出。