Die Rolle der Plastizität von Interneuronen bei der inhibitorischen Kontrolle von Zielbewegungen

关于兴奋性输入到新皮质GABA能抑制性中间神经元(INS)的可塑性如何与网络活动和自愿行为联系在一起，目前还知之甚少。我们在小鼠的初级运动前肢皮质(M1)的第2/3层和第5层解决了这个问题，过程中学习了一个新的皮质依赖、感觉触发的到达任务。对幼稚、未训练、清醒的小鼠的小白蛋白表达的周身抑制中间神经元(PVI)和规则的尖峰、兴奋性神经元的初步细胞外和全细胞记录表明，振动触觉刺激前爪在M1神经元中触发兴奋反应，但不触发前肢运动。然而，在受过训练的小鼠身上，这种反应会迅速转化为到达的运动指令，并随着到达的距离而扩大。有趣的是，PVI的兴奋性运动指令发生在兴奋性神经元之前，而且对M1 PVI的光遗传刺激可以诱发完整的REACH。总而言之，我们的数据表明，与M1功能的经典模型所提出的抑制运动输出相反，对PVI的兴奋性输入以及随后的PVI尖峰信号参与了自愿运动的释放。在这里，我们的目标是测试这一假设，即学习过程中对M1室旁路兴奋性输入的可塑性驱动了室旁路诱发的READH的招募。我们将在学习REACH前后进行细胞外和2-光子(2P)靶向记录，同时进行PVI和生长抑素表达的树突状抑制素(SOMI)的光遗传操作。此外，我们将使用我们在研究单位(RU)的合作者开发和测试的分子工具来标记和操作那些经历可塑性的IN，以直接将IN可塑性与M1电路动力学和REACH联系起来。

Little is known about how the plasticity of excitatory input to neocortical GABAergic inhibitory interneurons (INs) is linked to network activity and voluntary behavior. We address this question in layers 2/3 and 5 of the primary motor forelimb cortex (M1) of mice during learning a novel cortically-dependent, sensory-triggered, reaching task. Preliminary extracellular and whole-cell recordings of parvalbumin-expressing perisomatic inhibitory interneurons (PVIs) and regular spiking, excitatory, neurons in naïve, untrained, awake mice show that vibrotactile stimulation of the forepaw triggers an excitatory response in M1 neurons, but no forelimb movement. In trained mice, however, this response is rapidly transformed into a reaching motor command that scales with the distance reached. Intriguingly, the excitatory movement command in PVIs occurs before that in excitatory neurons, moreover optogenetic stimulation of M1 PVIs can evoke complete reaches. Together our data suggests that, rather than inhibiting motor output as proposed by classic models of M1 function, excitatory input to PVIs and subsequent PVI spiking is involved in the release of voluntary movements. Here, our goal is to test the hypothesis that plasticity of excitatory inputs to M1 PVIs during learning drives the recruitment of PVI-evoked reaching. We will perform extracellular and 2-Photon (2P) targeted recordings alongside optogenetic manipulations of PVIs and somatostatin-expressing dendritic inhibitory INs (SOMIs) before and after learning to reach. Moreover, we will use molecular tools developed and tested from our collaborators in the research unit (RU) to mark and manipulate those INs undergoing plasticity to directly link IN plasticity to M1 circuit dynamics and reaching.