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.

对新皮层GABA能抑制性中间神经元（INs）的兴奋性输入的可塑性如何与网络活动和自愿行为联系起来知之甚少。我们解决这个问题的第2/3层和第5层的初级运动前肢皮层（M1）的小鼠在学习一种新的皮质依赖性，感觉触发，达到任务。对表达小清蛋白的体周抑制性中间神经元（PVIs）和未接受过训练的清醒小鼠中规则尖峰兴奋性神经元的初步细胞外和全细胞记录显示，对前爪的振动触觉刺激触发M1神经元的兴奋性反应，但没有前肢运动。然而，在受过训练的老鼠中，这种反应迅速转化为一种运动指令，随着到达的距离而缩放。有趣的是，PVIs中的兴奋性运动命令发生在兴奋性神经元中的兴奋性运动命令之前，并且M1 PVIs的光遗传学刺激可以唤起完整的到达。总之，我们的数据表明，而不是抑制运动输出所提出的经典模型M1功能，兴奋性输入PVI和随后的PVI尖峰参与自愿运动的释放。在这里，我们的目标是测试的假设，即可塑性的兴奋性输入M1 PVIs在学习过程中驱动招聘PVI诱发的达到。我们将进行细胞外和2-光子（2 P）靶向记录以及PVIs和生长抑素表达树突抑制性IN（SOMIs）的光遗传学操作之前和之后学习达到。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纵那些经历可塑性的IN，以直接将IN可塑性与M1电路动力学和延伸联系起来。