Reorganization of the Central Visual System by Inhibitory Neuron Transplantation

通过抑制性神经元移植重组中枢视觉系统

基本信息

批准号：
10455415
负责人：
Gyorgy Lur
金额：
$ 48.25万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10455415
关键词：
Adolescent Adult Anatomy Base of the Brain Brain Calcium Cell Transplantation Cells Childhood Contralateral Corpus Callosum Data Development Dissection Embryo Equilibrium Glutamates Goals Housing Image Intuition Light Maps Measures Mediating Microscopy Modeling Mus Neurons Parvalbumins Pattern Pharmacology Regulation Resolution Role Sensory Slice Structure Supporting Cell Testing Thalamic structure Time Tissues Transplantation Viral Visual Visual Acuity Visual Cortex Visual impairment Visual system structure Whole-Cell Recordings area striata awake base brain dysfunction brain repair calcium indicator cell type chemical genetics critical period designer receptors exclusively activated by designer drugs experience in vivo inhibitory neuron insight monocular deprivation multiphoton imaging novel optogenetics rabies viral tracing relating to nervous system repair strategy response tool two-photon visual deprivation visual plasticity

项目摘要

The transplantation of embryonic inhibitory neurons has recently emerged as a promising avenue for cell-based brain repair. Previously, we and others have shown that transplanted inhibitory neurons restore juvenile plasticity to the circuits of adult visual cortex. In this study, we set out to elucidate the mechanisms for transplant-induced cortical plasticity. We hypothesize that transplanted inhibitory neurons reactivate plasticity by creating a new, disinhibitory microcircuit in recipient adult visual cortex. First, we will map out the effects of transplantation on the inter- and intralaminar balance of excitation and inhibition. Next, we will compare the cell-type specific effects of brief monocular deprivation on visual activity in host cortex. Lastly, we will test whether transplanted neurons make long-range connections with appropriate circuits. To evaluate these hypotheses, this proposal will take advantage of recent advances in optogenetic dissection of inhibitory circuits in brain slice, multiphoton imaging of defined cortical cell types using genetically encoded calcium indicators, chemical-genetic tools for testing the mechanisms of transplant- induced plasticity and viral tracing and whole brain clearing to identify the brain-wide connections onto transplanted cells. If successful, the proposed studies shed light on the mechanisms of transplant-induced cortical reorganization. These studies are also likely to give insight into the normal developmental regulation of cortical plasticity by inhibitory cells.

胚胎抑制神经元的移植最近已成为有前途的大道用于基于细胞的大脑修复。以前，我们和其他人已经表明移植的抑制性神经元将少年可塑性恢复到成人视觉皮层的电路。在这项研究中，我们着手阐明移植诱导的皮质可塑性的机制。我们假设移植的抑制性神经元通过在受体成人视觉皮层中创建新的抑制性微电路来重新激活可塑性。首先，我们会的绘制移植对激发和抑制的层间和腔内平衡的影响。接下来，我们将比较短暂单眼剥夺对宿主视觉活动的细胞类型的特定影响皮质。最后，我们将测试移植神经元是否与适当的电路。为了评估这些假设，该提案将利用近期光学遗传学的优势脑切片中抑制回路的解剖，使用定义的皮质细胞类型的多光子成像遗传编码的钙指标，用于测试移植机制的化学遗传学工具 - 诱导的可塑性和病毒追踪和整个大脑清除，以识别脑范围的连接移植细胞。如果成功，则提出的研究阐明了移植诱导的机制皮质重组。这些研究也可能会深入了解正常发展通过抑制细胞调节皮质可塑性。