CAREER: Opposing roles of cortical input to dorsal striatum

职业：皮质输入与背侧纹状体的相反作用

• 批准号: 1845355
• 负责人: David Margolis
• 金额: $ 90万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845355&HistoricalAwards=false
• 关键词: CAREER; Opposing; roles; cortical; input

In order to feel, think, move, and learn, different areas of the brain must communicate with each other through synaptic connections. The interactions between sensory and motor areas of the brain are particularly important for interacting with and reacting to the world around us. However, it is still unknown exactly how neural signaling from the sensory areas of the brain directly influence brain areas related to movement. The goal of this neuroscientific study is to understand how signals from sensory and motor areas of the cerebral cortex combine within a important subcortical area called the striatum to influence decision-making behavior in mice. Conducting the studies in mice allows for the use of innovative neuroscience technology for discovering the mechanistic basis of brain function on the level of synapses, neural circuits, and behavior. Classroom and outreach components of the project are designed to build on the technological and scientific themes of the research. A university course based on open source neurotechnology will enable students to achieve fluency in modern experimental neuroscience and skills they can use throughout their careers. The outreach program will strengthen ties with underrepresented minorities through international exchange with researchers in Mexico and through bilingual publications in a scientific journal for kids. Together, this project will advance our understanding and appreciation of brain function on multiple levels, from cutting-edge research and education to beneficial societal outreach. The integration of sensory and motor information is critical for discriminating between different stimuli and making appropriate actions. This projects investigates how single neurons and neural circuits within key brain areas, such as the dorsal striatum, dynamically process sensory and motor input during behavioral performance and during learning. In the mouse whisker-related somatosensory system, axonal projections of primary sensory cortex (S1) and primary motor cortex (M1) combine at the level of the dorsal striatum, a structure known for its role in behavior through influence on the motor thalamus. The role of S1 in striatal function, and how S1 and M1 inputs combine, is unknown. Most previous work has focused on frontal cortex inputs to striatum, and therefore, our understanding of how sensorimotor integration takes place in striatum, and what its role is during behavior and learning are incomplete. The goal of this CAREER project is to determine the neural circuitries underlying S1 and M1 input to dorsal striatum, and to define their roles in behavior. The results will provide important knowledge of the distinct roles of S1- and M1-corticostriatal signaling in behavior. The education component promotes expertise in neurotechnology for undergraduate and graduate students, while outreach to underrepresented minorities builds on essential elements of the research program through international exchange and youth-focused bilingual publications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

为了感觉、思考、移动和学习，大脑的不同区域必须通过突触连接相互沟通。大脑感觉和运动区域之间的相互作用对于我们与周围世界的互动和反应尤为重要。然而，来自大脑感觉区域的神经信号是如何直接影响与运动相关的大脑区域的，目前尚不清楚。这项神经科学研究的目标是了解来自大脑皮层的感觉和运动区域的信号如何在一个重要的皮层下区域纹状体内结合，从而影响小鼠的决策行为。在老鼠身上进行的研究允许使用创新的神经科学技术来发现突触、神经回路和行为水平上大脑功能的机制基础。项目的课堂和外展部分旨在建立在研究的技术和科学主题之上。一门基于开源神经技术的大学课程将使学生能够流利地掌握现代实验神经科学和技能，这些技能可以在他们的职业生涯中使用。外联项目将通过与墨西哥研究人员的国际交流以及在儿童科学期刊上发表双语出版物，加强与代表性不足的少数民族的联系。总之，这个项目将在多个层面上推进我们对大脑功能的理解和欣赏，从前沿研究和教育到有益的社会推广。感觉和运动信息的整合对于区分不同的刺激并做出适当的行动至关重要。该项目研究了在行为表现和学习过程中，大脑关键区域（如背纹状体）内的单个神经元和神经回路是如何动态处理感觉和运动输入的。在小鼠须相关体感觉系统中，初级感觉皮层（S1）和初级运动皮层（M1）的轴突投射在背纹状体水平结合，背纹状体是一种通过影响运动丘脑而在行为中起作用的结构。S1在纹状体功能中的作用，以及S1和M1输入如何结合，目前尚不清楚。以往的工作大多集中在额叶皮层对纹状体的输入，因此，我们对纹状体中感觉运动整合如何发生，以及它在行为和学习中的作用的理解是不完整的。本CAREER项目的目标是确定S1和M1向背纹状体输入的神经回路，并确定它们在行为中的作用。该结果将提供S1-和m1皮质纹状体信号在行为中的不同作用的重要知识。教育部分促进本科生和研究生在神经技术方面的专业知识，同时通过国际交流和以青年为重点的双语出版物，向未被充分代表的少数民族伸出援助之手，建立在研究项目的基本要素之上。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

• DOI: 10.1016/j.cub.2019.03.028
• 发表时间: 2018-10
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Christian R. Lee;Alex J. Yonk;J. Wiskerke;K. Paradiso;J. Tepper;David J. Margolis

FosGFP expression does not capture a sensory learning-related engram in superficial layers of mouse barrel cortex

• DOI: 10.1073/pnas.2112212118
• 发表时间: 2021-12-28
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Lee, Jiseok;Urban-Ciecko, Joanna;Barth, Alison L.
• 通讯作者: Barth, Alison L.