Imaging progressive circuit reorganization after traumatic brain injury

脑外伤后进行性回路重组的成像

• 批准号: 10678271
• 负责人: Alexa Marie Tierno
• 金额: $ 4.28万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678271
• 关键词: Acute; Affect; Anatomy; Animals; Area; Award; Behavior; Brain; Brain Injuries; Brain region; Calcium; Cell Culture Techniques; Cells; Cessation of life; Chronic; Code; Communities; Complement; Complex; Computer Analysis; Deafferentation procedure; Dedications; Disease; Embryo; Epilepsy; Evaluation; Functional disorder; Germ Cells; Goals; Hippocampus; Human; Image; Impairment; Injury; Institution; International; Interneurons; Knowledge; Laboratories; Lateral; Learning; Light; Literature; Maintenance; Maps; Medial; Memory; Mentorship; Microscope; Mus; Nervous System Trauma; Neuroanatomy; Neurobiology; Neurons; Neurophysiology - biologic function; Neurosciences; Output; Persons; Physiology; Pre-Clinical Model; Precision therapeutics; Property; Publishing; Rattus; Recurrence; Reporting; Research; Research Personnel; Risk; Rodent; Rodent Model; Role; Scientist; Seizures; Synapses; TBI treatment; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Training; Translating; Transplantation; Traumatic Brain Injury; Viral; Visualization; Vocational Guidance; Work; basal forebrain; career; cell type; cognitive disability; entorhinal cortex; excitatory neuron; experimental study; fluid percussion injury; gamma-Aminobutyric Acid; hippocampal pyramidal neuron; in vivo; in vivo calcium imaging; induced pluripotent stem cell; inhibitory neuron; injured; migration; mouse model; neural circuit; neurophysiology; novel; place fields; postsynaptic; presynaptic; prevent; progenitor; response; spinal cord and brain injury; stem cells

PROJECT SUMMARY/ABSTRACT Traumatic brain injury (TBI) can lead to cognitive disabilities and epilepsy, but circuit mechanisms remain unknown. I hypothesize that the death of inhibitory interneurons and subsequent reorganization of neural circuitry in hippocampus leads to post-traumatic deficits in spatial coding and memory. To test this, I propose studies to systematically and comprehensively map the progressive structural and functional breakdown of hippocampal neurons in a widely used mouse model of TBI. In Aim 1, I will use advanced whole-brain circuit mapping technologies to visualize the inputs and outputs of hippocampal CA1 neurons in control and brain injured animals. In Aims 2 and 3, I will use calcium imaging with miniature microscopes to determine how spatial coding in hippocampus is altered by TBI and after interneuron transplantation. My long term goal is to build an independent academic career dedicated to developing novel circuit-based therapeutics for brain and spinal cord injury. Achieving this goal will require extensive training in the principles of neurotrauma, physiology and behavior. UCI is an outstanding institution for training in these areas, primarily due to the rich community of prominent neuroscientists and clinicians performing neurotrauma research and the pioneering role of UCI in the neurobiology of learning and memory, epilepsy and behavior. To help me achieve my goals, I have assembled a world-class team of internationally recognized scientists who will provide me with hands-on technical training, formal coursework and career guidance during the award and beyond.

项目总结/摘要 创伤性脑损伤（TBI）可导致认知障碍和癫痫，但电路机制仍然存在 未知我假设抑制性中间神经元的死亡和随后的神经元重组 海马体中的回路导致空间编码和记忆的创伤后缺陷。为了验证这一点，我建议 研究，以系统和全面地绘制逐步结构和功能崩溃的 海马神经元在广泛使用的TBI小鼠模型。在目标1中，我将使用先进的全脑电路 映射技术，以可视化控制和大脑中海马CA 1神经元的输入和输出 受伤的动物在目标2和3中，我将使用微型显微镜进行钙成像，以确定 海马中的空间编码被TBI和中间神经元移植后改变。我的长期目标是 建立一个独立的学术生涯，致力于开发新的基于电路的治疗大脑， 脊髓损伤实现这一目标将需要广泛的培训原则的神经创伤，生理 和行为。UCI是这些领域的优秀培训机构，主要是由于丰富的社区 杰出的神经科学家和临床医生进行神经创伤研究和UCI的开拓性作用， 学习和记忆、癫痫和行为的神经生物学。为了帮助我实现目标，我 我组建了一个由国际公认的科学家组成的世界级团队， 技术培训，正式课程和职业指导期间及以后。