Mechanisms of Somatosensory Circuit Remapping After Cortical Injury in Mice

小鼠皮质损伤后体感回路重新映射的机制

基本信息

批准号：
10655600
负责人：
William Abel Zeiger
金额：
$ 24.21万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10655600
关键词：
Ablation Animal Model Animals Area Atlases Behavioral Biological Models Brain Brain Mapping Brain region Calcium California Cell Shape Cells Central Nervous System Clinical Sciences Communities Complex Control Animal Dendritic Spines Development Development Plans Equilibrium Etiology Exhibits Functional Magnetic Resonance Imaging Functional disorder Future Gene Expression Global Change Goals Human Image Imaging Techniques Impairment Individual Injury Institution Interneurons Knowledge Label Learning Lesion Light Los Angeles Maps Measures Mediating Mentors Methods Movement Disorders Mus Nervous System Trauma Neurology Neurons Neurosciences Parvalbumins Pathologic Pathologic Processes Physicians Play Positron-Emission Tomography Pyramidal Cells Recovery Recovery of Function Research Research Personnel Resolution Resources Role Scientist Sensory Shapes Site Somatosensory Cortex Stroke Technical Expertise Testing Therapeutic Time Tissues Translational Research Universities Vibrissae Work axonal sprouting career career development designer receptors exclusively activated by designer drugs disability experience human model improved in vivo in vivo calcium imaging insight mouse model nervous system disorder neural circuit neuronal circuitry neuroregulation novel post stroke professor response sensory cortex sensory discrimination somatosensory stroke model translational study two-photon whisker discrimination

项目摘要

PROJECT SUMMARY / ABSTRACT Circuits in the healthy central nervous system (CNS) have the capacity for reorganization and remapping of functionality. Growing evidence suggests that circuit remapping may contribute to a number of neurologic diseases as well. For example, it has been widely hypothesized that remapping of circuits underlies recovery after a focal lesion of the CNS, such as stroke. However, how specific changes in neuronal circuits mediate improvement in function and recovery after cortical injury remains a major gap in our understanding. Here, Dr. Zeiger will utilize advanced techniques for imaging and manipulating circuits in vivo to define the local and global changes in neural circuits that occur following a lesion of the somatosensory cortex in mice. In Aim 1, Dr. Zeiger will investigate the role of GABAergic parvalbumin (PV) cells in peri-lesional remapping of somatosensory function after small lesions to the cortex. PV cells shape cortical sensory representations and regulate experience-dependent plasticity. Dr. Zeiger hypothesizes that PV cells in peri-lesional cortex play a critical role in functional remapping. He will test this hypothesis by 1) recording sensory-evoked responses from PV and pyramidal cells throughout recovery using in vivo two-photon (2P) calcium imaging and 2) modulating PV cell activity using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and measuring the effects on circuit remapping. In Aim 2, Dr. Zeiger will identify novel candidate brain regions for remapping of lost functionalities that mediate behavioral recovery after large cortical lesions. He hypothesizes that remapping after large lesions involves distributed networks of neurons across multiple brain regions. He will test this by generating a quantitative atlas of all remapped whisker-responsive neurons following recovery, allowing identification of novel candidate regions important for remapping. He will then measure changes in circuit function in these sites over time during recovery and confirm the roles of these regions by manipulating neuronal activity with DREADDs and testing the effect on recovery of somatosensory function. Dr. Zeiger is currently an Assistant Professor in Neurology at the University of California – Los Angeles (UCLA). His long-term career goal is to work as a physician-scientist investigating mechanisms of circuit dysfunction contributing to neurologic disease. As part of this proposal he will carry out a detailed career development plan focusing on gaining technical skills in advanced neuroscience methods for investigating neuronal circuits, expanding his knowledge of how circuit dysfunction contributes to movement disorders, and transitioning to an independent career. This work will be carried out at UCLA, a renowned research institution with an extensive community of investigators in neuroscience and neurology and supported by numerous institutional resources such as the UCLA Clinical and Translational Science Institute. Dr. Zeiger’s career development will be guided by a team of mentors including his primary mentor Dr. Carlos Portera-Cailliau and co-mentors Dr. Jeff Bronstein and Dr. S. Thomas Carmichael.

项目摘要 /摘要健康中枢神经系统（CNS）中的电路具有重组的能力和重新映射功能。越来越多的证据表明，电路重新映射可能有助于多种神经系统疾病也是如此。例如，已经广泛假设电路的重新映射是恢复的基础在CNS的局灶性病变（例如中风）之后。但是，神经元电路的特定变化如何介导皮质损伤后功能和恢复的改善仍然是我们理解的主要差距。在这里，博士 Zeiger将利用先进的技术在体内进行成像和操纵电路来定义本地和全球小鼠体感皮质病变后发生的神经回路的变化。在AIM 1中，Zeiger博士将研究GABA能和蛋白（PV）细胞在体感的元素重新映射中的作用小病变到皮质后的功能。 PV细胞塑造皮质感觉表示并调节依赖经验的可塑性。 Zeiger博士假设，在静脉内皮层中的PV细胞起着至关重要的作用在功能重新映射中。他将通过1）记录来自PV和使用体内两光子（2p）钙成像和2）调节PV细胞的锥体细胞在整个恢复过程中恢复整个恢复使用Dreadds（专门由设计师药物激活的设计器受体）的活动并测量对电路重新映射的影响。在AIM 2中，Zeiger博士将确定新颖的候选大脑区域以重新映射丢失大型皮质病变后介导行为恢复的功能。他假设此之后重新映射大型病变涉及多个大脑区域的神经元的分布网络。他将通过恢复后，生成所有重新映射的晶须响应神经元的定量地图集，允许识别新型候选区域对于重建很重要。然后，他将测量电路功能的变化在恢复过程中随着时间的推移这些地点，并通过操纵神经元活动确认这些区域的作用通过恐怖分子并测试对体感功能恢复的影响。 Zeiger博士目前是加利福尼亚大学神经病学助理教授 - 洛杉矶（UCLA）。他的长期职业目标是作为巡回赛的身体科学家调查机制功能障碍导致神经系统疾病。作为该提议的一部分，他将进行详细的职业开发计划的重点是获得高级神经科学方法的技术技能神经元电路，扩大了他对电路功能障碍如何促进运动障碍的了解，以及过渡到独立职业。这项工作将在著名的研究机构UCLA进行在神经科学和神经病学领域的广泛调查员社区，并得到许多支持 UCLA临床和转化科学学院等机构资源。齐格尔博士的职业开发将由一组导师的指导，包括他的主要导师Carlos Portera-Cailliau博士和杰夫·布朗斯坦（Jeff Bronstein）博士和S. Thomas Carmichael博士。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High-Sensitivity Intrinsic Optical Signal Imaging Through Flexible, Low-Cost Adaptations of an Upright Microscope.

DOI：
10.1523/eneuro.0046-23.2023
发表时间：
2023-07
期刊：
ENEURO
影响因子：
3.4
作者：
Vasquez, Brenda;Campos, Baruc;Cao, Ashley;Theint, Aye Theint;Zeiger, William
通讯作者：
Zeiger, William