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

局部环路抑制中间神经元在塑造皮层环路的时序和兴奋性方面的作用已经得到了很好的证实。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中心作用，这一重要细胞类型的丢失或失调与认知和运动缺陷有关也就不足为奇了。到目前为止，只有通过应用转基因动物才有可能可靠地针对抑制性中间神经元进行基因修饰。非人类灵长类动物作为认知和精细运动技能的主要模型，不适用于转基因工具。基因转移载体技术的最新进展使基因传递更有效，也更具细胞类型特异性。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，特别是小白蛋白和生长抑素阳性神经元。这样，我们将为包括非人类灵长类在内的非转基因动物提供特定细胞类型的光遗传操作。配备了这种新的靶向方法，我们的目标是研究抑制神经元在产生神经振荡和控制运动中的作用。

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.