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Cell-type specific optogenetic manipulation for characterizing the role of inhibitory interneurons in motor cortex of non-transgenic animals

细胞类型特异性光遗传学操作用于表征非转基因动物运动皮层中抑制性中间神经元的作用

基本信息

批准号：
237887746
负责人：
Professor Dr. Christian Buchholz
金额：
--
依托单位：
Biotech Research and Innovation Centre (BRIC)
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/237887746?language=en
关键词：
Cell type specific optogenetic manipulation

项目摘要

The role for local circuit inhibitory interneurons in shaping the timing and excitability of cortical circuits is well established. Inhibitory interneurons control cellular and network synchronization and output by dictating and coordinating action potential generation. Given the central role for interneurons in the function of the central nervous system it comes as no surprise that loss or dis-regulation of this important cell type has been implicated in cognitive and motor defects. So far, it has only been possible to reliably target genetic modifications to inhibitory interneurons by applying transgenic animals. Non-human primates as the prime model of cognition and fine motor skills are not amenable for transgenic tools. Recent progress in gene transfer vector technology has made gene delivery more efficient and also more cell type specific. We aim at generating recombinant viruses that will deliver genes precisely to inhibitory neurons with a special focus on parvalbumin and somatostatin positive neurons. This way, we will make optogenetic manipulations of specific cell types available for non-transgenic animals including non-human primates. Equipped with this new targeting method we aim to investigate the role of inhibitory neurons in generating neural oscillations and controlling movements.

局部回路抑制性中间神经元在塑造皮层回路的时序和兴奋性中的作用已经得到很好的确立。抑制性中间神经元通过支配和协调动作电位的产生来控制细胞和网络的同步和输出。鉴于中间神经元在中枢神经系统功能中的核心作用，这一重要细胞类型的丢失或失调与认知和运动缺陷有关就不足为奇了。到目前为止，只有通过应用转基因动物才有可能可靠地将基因修饰靶向抑制性中间神经元。非人灵长类动物作为认知和精细运动技能的主要模型不适合转基因工具。基因转移载体技术的最新进展使基因递送更有效，也更具有细胞类型特异性。我们的目标是产生重组病毒，将基因精确地传递到抑制性神经元，特别关注小清蛋白和生长抑素阳性神经元。这样，我们将使特定细胞类型的光遗传学操作可用于非转基因动物，包括非人灵长类动物。配备了这种新的靶向方法，我们的目标是研究抑制性神经元在产生神经振荡和控制运动中的作用。