Neuroelectronic and optogenetic stimulation for the precise control of corticospinal plasticity

通过神经可塑性，成人大脑具有不断适应和形成新回路的奇妙能力。当我们背诵课文或练习乐器时，我们会利用这一现象。正如“熟能生巧”这句话所说明的那样，重复一种活动是巩固这种活动的关键因素。多项研究表明，神经活动的重复可以导致突触增强，遵循赫布在60多年前确定的原则，通常被概括为“一起放电、连接在一起的神经元”。尽管我们对依赖活动的突触可塑性的理解取得了进展，但我们仍然对其在体内大规模系统中表达的基本原理知之甚少。*我的研究计划的总体目标是确定神经元活动如何导致连接性的变化并影响大脑功能。我特别感兴趣的是研究负责运动控制的回路中的重复活动如何导致皮质功能图的重组。运动系统是一个很好的结构，使我们能够理解导致功能重组的原理，因为我们可以从肌肉活动的角度直接观察它的输出。为了研究这些原理，我将使用尖端的神经工程技术来精确控制皮质脊髓回路的活动模式。在实验室里，我将在大鼠身上测试干预措施，将大规模录音与电和光遗传刺激相结合。这些干预措施的目的是确定有效的参数组合，以诱导连接皮质神经元和运动前肢肌肉的回路发生变化。通过这项研究，我将找出神经元活动导致系统尺度功能变化的规律和指导神经可塑性的有效方法。

Through neuroplasticity, the adult brain has the wonderful ability to continually adapt and form new circuits. We take advantage of this phenomenon when we memorize a text or when we practice a musical instrument. As the phrase "practice makes perfect” illustrates, repeating an activity is the key element that allows its consolidation. Several studies have shown that the repetition of neural activity can lead to synaptic potentiation following the principles identified by Hebb more than sixty years ago, often summarized as "neurons that fire together, wire together”. Despite progress in our understanding of activity-dependent synaptic plasticity, we still understand very little about the principles underlying its expression in large-scale in vivo systems.******The overall aim of my research program is to identify how neuronal activity can cause changes in connectivity and influence brain function. I am particularly interested in studying how the repetition of activity in circuits responsible for the control of movements can lead to the reorganization of cortical functional maps. The motor system is a great structure to enable us to understand the principles leading to functional reorganization, because we can directly observe its output in terms of muscle activity.****** To study these principles, I will employ cutting-edge neuroengineering techniques to precisely control patterns of activity in corticospinal circuits. In the laboratory, I will test interventions in rats combining large-scale recordings with the electrical and optogenetic stimulation. These interventions will aim to identify effective combinations of parameters to induce changes in the circuits that link the cortical neurons to motor forelimb muscles. Through this research, I will identify the rules by which neuronal activity leads to system-scale functional changes and effective methods to guide neuroplasticity.