Imaging progressive circuit reorganization after traumatic brain injury

项目摘要/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重组 海马体中的回路会导致创伤后的空间编码和记忆缺陷。为了测试这一点，我建议 系统和全面地绘制渐进性结构和功能细分图的研究 一种广泛使用的脑外伤小鼠模型的海马神经元。在目标1中，我将使用先进的全脑电路 可视化对照和脑内海马CA1区神经元输入和输出的标测技术 受伤的动物。在目标2和目标3中，我将使用带有微型显微镜的钙成像来确定如何 颅脑损伤后和神经元间移植后，海马区的空间编码发生改变。我的长期目标是 建立独立的学术生涯，致力于开发脑部和脑部的新型电路疗法 脊髓损伤。要实现这一目标，需要对神经创伤、生理学的原理进行广泛的培训 和行为。UCI在这些领域是一家杰出的培训机构，主要得益于富裕的社区 杰出的神经学家和临床医生进行神经创伤研究，以及UCI在 学习和记忆、癫痫和行为的神经生物学。为了帮助我实现我的目标，我有 组建了一支由国际知名科学家组成的世界级团队，他们将为我提供实践经验 在获奖期间及以后，技术培训、正式课程和职业指导。

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.