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（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在一起，我们知之甚少。我们在小鼠学习一项新的皮质依赖、感觉触发、到达任务时，在初级运动前肢皮层（M1）的第2/3层和第5层中解决了这个问题。在naïve未训练的清醒小鼠中，表达parvalbumin的细胞外和全细胞记录显示，前爪的振动触觉刺激会触发M1神经元的兴奋反应，但不会引起前肢运动。然而，在经过训练的小鼠中，这种反应会迅速转化为一种随到达距离而变化的到达运动命令。有趣的是，PVIs的兴奋性运动指令发生在兴奋性神经元之前，并且光遗传刺激M1 PVIs可以引起完整的到达。综上所述，我们的数据表明，与经典M1功能模型所提出的抑制运动输出不同，对PVI的兴奋性输入和随后的PVI尖峰参与了随意运动的释放。在这里，我们的目标是验证学习过程中兴奋性输入M1 pvi的可塑性驱动pvi诱发到达的招募这一假设。我们将在学习到达之前和之后进行细胞外和2光子（2P）靶向记录，以及光遗传学操作PVIs和表达生长抑素的树突状抑制性INs （SOMIs）。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正在进行塑性的in，以直接将in塑性与M1电路动力学和到达联系起来。