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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

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