Neuroelectronic and optogenetic stimulation for the precise control of corticospinal plasticity

通过神经可塑性，成年人的大脑具有持续适应和形成新回路的奇妙能力。当我们记忆课文或练习乐器时，我们会利用这种现象。正如“熟能生巧”这句话所说明的那样，重复一项活动是使其得以巩固的关键因素。几项研究表明，神经活动的重复可以导致突触增强，遵循Hebb在60多年前确定的原则，通常被总结为“神经元一起激发，连接在一起”。尽管我们对活动依赖性突触可塑性的理解取得了进展，但我们对它在大规模体内系统中表达的基本原理仍然知之甚少，我的研究计划的总体目标是确定神经元活动如何引起连接的变化并影响大脑功能。我特别感兴趣的是研究负责控制运动的回路中的活动重复如何导致皮层功能图的重组。运动系统是一个伟大的结构，使我们能够理解导致功能重组的原则，因为我们可以直接观察肌肉活动的输出。为了研究这些原理，我将采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。在实验室中，我将测试大鼠的干预措施，将大规模记录与电和光遗传学刺激相结合。这些干预措施旨在确定有效的参数组合，以诱导连接皮层神经元和运动前肢肌肉的回路发生变化。通过这项研究，我将确定神经元活动导致系统规模的功能变化的规则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.