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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深部脑结构，似乎在人类和鸟类的运动序列学习中发挥类似的功能。尽管目前人类的治疗方法涉及长期植入BG结构的电极刺激，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通路，完全致力于单一任务-歌曲学习。在完成鸣禽BG不同细胞类别的第一次记录后（Goldberg and Fee, 2010; Goldberg et al., 2010），我现在准备提出BG功能的基本问题：丘脑如何处理BG输出？不同的BG细胞类如何实现运动学习？BG回路中的神经相互作用是什么？在本提案中，我概述了实现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来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回路中不同的细胞类别。在医学院，我接受了基底神经节相关神经系统疾病患者护理方面的培训，在博士后培训的第一阶段，我学习了从自由运动动物基底神经节连接的神经元进行记录。在这份建议书中制定的培训计划是专门为我提供新的技术，使我能够进行新的实验，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调节范式所需的计算数字信号处理技能，开发一种新的方法，在行为过程中同时记录多个神经元的细胞外记录，并学习使用最近开发的细胞内微驱动器来记录细胞内自由运动的动物。这些目标将在2011年秋季申请职位之前完成。当我掌握了这些技术，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来自BG和皮层的两个主要输入，通过记录连接的苍白质和丘脑神经元，以及在唱歌过程中记录反方向识别的皮质丘脑投射神经元。接下来，我将通过将神经记录与一种新的条件听觉反馈范例相结合，在实验控制的运动学习过程中检查BG输出信号，这种范例可以诱导快速的试错歌曲学习。最后，我将着手一项长期项目，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。这一最终目标包括开发一种记录鸣禽细胞内BG神经元的技术，并构成了我将在迈克尔·费（michael Fee）的支持下，在这项拨款的R00阶段继续进行的研究项目。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michael Fee实验室进行，在那里，我周围有才华横溢的研究生、博士后和教职员工。该系每周两次的系列研讨会，世界知名的演讲者和一流的设施非常令人兴奋。最后，尽管michael资金充足（两个r01），但我是实验室里仅有的两个博士后之一。这意味着迈克尔和我对彼此非常投入，我们经常每天花几个小时在一起，讨论实验，写论文和建造新设备。作为重新申请拨款的一部分，迈克尔和我仔细制定了实验、训练计划和独立之路，他同意在我过渡到R00阶段时亲自训练和支持我，那时我将开始研究特定纹状体和苍白质细胞类别在BG功能中的作用。这些努力的时间表将构成我进步的基准，在本提案的职业目标部分提出。