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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：
10612066
负责人：
Gyorgy Lur
金额：
$ 48.97万
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 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612066
关键词：
Adolescent Adult Anatomy Brain Calcium Cell Transplantation Cells Childhood Contralateral Corpus Callosum Darkness Data Development Dissection Embryo Embryo Transfer Equilibrium Glutamates Goals Housing Image Intuition Light Maps Measures Mediating Microscopy Modeling Mus Neurons Parvalbumins Pattern Regulation Resolution Role Sensory Slice Structure Supporting Cell Testing Thalamic structure Time Tissues Transplantation Viral Visual Visual Acuity Visual Cortex Visual System Visual impairment Whole-Cell Recordings area striata awake brain based brain dysfunction brain repair calcium indicator cell cortex cell type chemical genetics critical period designer receptors exclusively activated by designer drugs experience in vivo inhibitory neuron insight monocular deprivation multiphoton imaging neural novel optogenetics pharmacologic rabies viral tracing 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.

胚胎抑制神经元移植最近成为一种有前途的途径用于基于细胞的大脑修复。此前，我们和其他人已经证明，移植的抑制性神经元恢复成人视觉皮层回路的青少年可塑性。在这项研究中，我们着手阐明移植引起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去抑制微电路来重新激活可塑性。首先，我们将绘制移植对兴奋和抑制的层间和层内平衡的影响。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特异性影响皮质。最后，我们将测试移植的神经元是否与适当的神经元建立长距离连接。电路。为了评估这些假设，该提案将利用光遗传学的最新进展脑切片中抑制电路的解剖，使用确定的皮质细胞类型的多光子成像基因编码的钙指示剂，用于测试移植机制的化学遗传工具诱导可塑性、病毒追踪和全脑清除，以识别全脑连接移植的细胞。如果成功，拟议的研究将揭示移植诱导的机制皮质重组。这些研究也可能深入了解正常发育抑制细胞对皮质可塑性的调节。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Juvenile depletion of microglia reduces orientation but not high spatial frequency selectivity in mouse V1.

DOI：
10.1038/s41598-022-15503-0
发表时间：
2022-07-27
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Velez, Dario X. Figueroa;Arreola, Miguel;Huh, Carey Y. L.;Green, Kim;Gandhi, Sunil P.
通讯作者：
Gandhi, Sunil P.

Functional Differentiation of Mouse Visual Cortical Areas Depends upon Early Binocular Experience.

小鼠视觉皮层区域的功能分化取决于早期的双眼经验。

DOI：
10.1523/jneurosci.0548-20.2020
发表时间：
2021
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Salinas,KirstieJ;Huh,CareyYL;Zeitoun,JackH;Gandhi,SunilP
通讯作者：
Gandhi,SunilP

Host interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex.