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

中间神经元可塑性在目标运动抑制控制中的作用

• 批准号: 262041063
• 负责人: Professor Dr. James F.A. Poulet, Ph.D.
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/262041063?language=en
• 关键词: Die; Rolle; der; Plastizit; von

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.

关于新皮质 GABA 能抑制性中间神经元 (IN) 的兴奋性输入的可塑性与网络活动和自主行为之间的关系知之甚少，我们在小鼠初级运动前肢皮层 (M1) 的 2/3 层和 5 层中解决了这个问题。学习一种新颖的皮质依赖性、感觉触发的、表达小清蛋白的周围抑制性中间神经元的初步细胞外和全细胞记录。 (PVI) 和天真的、未经训练的清醒小鼠中的定期尖峰、兴奋性神经元表明，前爪的振动触觉刺激会触发 M1 神经元的兴奋性反应，但在经过训练的小鼠中，这种反应会迅速转化为前肢运动。有趣的是，PVI 中的兴奋性运动命令发生在兴奋性神经元中，而且 M1 的光遗传学刺激也更早。我们的数据表明，PVI 的兴奋性输入和随后的 PVI 尖峰并不像 M1 功能的经典模型所提出的那样抑制运动输出，而是参与随意运动的释放。假设学习过程中 M1 PVI 的兴奋性输入的可塑性驱动了 PVI 诱发到达的招募，我们将在光遗传学操作的同时进行细胞外和 2 光子 (2P) 靶向记录。此外，我们将使用研究单位（RU）的合作者开发和测试的分子工具来标记和操纵那些经历可塑性的 IN，以直接连接 IN。 M1电路的可塑性和动态性达到了。