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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）回路是一组临床相关的脑深部结构，似乎在人类和鸟类中发挥类似的功能-运动序列学习。尽管目前人类的治疗涉及长期植入BG结构的电极的刺激，但我们仍然不了解电信号如何通过电路传播以影响行为。鸣禽有专门的BG途径，完全致力于单一任务歌曲学习。在鸣禽BG中进行了来自不同细胞类别的第一次记录（Goldberg和Fee，2010; Goldberg等人，2010），我现在准备问BG功能的基本问题：BG输出如何在丘脑中处理？不同的BG细胞类别如何实现运动学习？BG回路中的神经相互作用是什么？在这个建议中，我概述了我的长期目标的路径：建立一个实验室，利用鸣禽模型系统的优势，研究基底神经节微电路如何促进正常和异常的运动功能。在我的博士论文中，我使用细胞生理学和双光子成像来研究皮层微电路中不同的细胞类别。在医学院，我接受了治疗基底神经节相关神经系统疾病患者的培训，在博士后培训的第一阶段，我学会了记录自由运动动物基底神经节中连接的神经元。本建议书中制定的培训计划旨在为我带来新的技术，使我能够执行新的实验并过渡到独立的职位。例如，我的近期目标是学习实现一种新的歌曲条件反射范式所需的计算和数字信号处理技能，开发一种在行为过程中同时从多个神经元进行细胞外记录的新方法，并学习使用最近开发的细胞内微驱动器记录自由移动动物的细胞内。这些目标将在我申请2011年秋季职位之前的辅导阶段完成。当我掌握这些技术时，我将能够解决基底神经节和丘脑功能的基本问题。首先，我将研究运动丘脑如何整合其两个主要的输入，从BG和皮质，通过记录从连接的苍白球和丘脑神经元，并记录从逆行识别皮质丘脑投射神经元在唱歌。接下来，我将研究BG输出信号在实验控制的运动学习相结合的神经记录与一种新的条件听觉反馈范式，诱导快速试错歌曲学习。最后，我将开始一个长期项目，研究六种主要BG细胞类别中的每一种在这种学习过程中如何改变其活动，以及这些神经元在行为过程中如何相互作用。这最终的目标包括一种技术的发展，以记录从BG神经元在唱歌的鸟类细胞内，并构成了研究计划，我将继续，与Michale费的支持下，在R 00阶段的这笔赠款。这项培训和研究将在麻省理工学院麦戈文脑与认知科学研究所的Michale Fee实验室进行，在那里我被才华横溢的研究生，博士后和教师包围。该部门是非常刺激的两个每周研讨会系列，世界知名的演讲者和一流的设施。最后，尽管Michale资金充足（两个R 01），但我是实验室仅有的两个博士后之一。这意味着Michale和我彼此非常投入，我们每天经常花几个小时在一起，讨论实验，写论文和构建新设备。作为重新申请资助的一部分，Michale和我仔细制定了实验、训练计划和独立的道路，他同意在我过渡到R 00阶段时亲自训练和支持我，那时我将开始追求特定的纹状体和苍白球细胞类在BG功能中发挥的作用。这些努力的时间轴将构成我的进展基准，在本建议书的职业目标部分中列出。