Dissecting the contributions of activity in specific neural populations to motor control using closed-loop optogenetic manipulations

摘要 理解行为和运动控制背后的神经回路机制的能力至关重要 依赖于我们可逆地调节功能神经回路活动的能力，而且是用单细胞 精确度。该项目将对项目1-4的预测进行因果检验，并反过来通知模型、数据 其他项目2-4的分析和数据收集。对电路机制有一个清晰的了解 在运动控制的基础上，细胞特有的皮质和皮质下区域将通过光遗传操纵 使用闭环范例直接评估特定神经群体的贡献，或 关于运动控制的特定类型的活动动力学。我们将使用三种类型的闭环式运算范例： I)闭环范例，其中我们以光遗传方式操纵特定神经元群体的活动 基于行为状态，ii)闭环范例，其中我们通过光遗传来操纵 基于其活动的特定神经元群体，以及iii)其中神经活动 会产生特定的行为结果。我们将测试皮质和皮质下区域对 特定CSN群体的活动和通过触发光遗传操作的运动行为 行为的特定时代。我们还将通过使用以下方法来表征功能识别神经元的角色 由神经活动模式触发的全息光遗传操作。最后，我们将使用光学 研究上游神经种群如何贡献的闭环式可操作脑-机器范例 运动皮质中皮质脊髓神经元与非皮质脊髓神经元的活动。这些实验将检验 通过多种方法，相同的假设，并将使我们能够建立因果关系 不同区域的神经活动与神经活动和行为之间的关系。他们将提供毫无价值的 对具有特定投射模式或特定投射模式的特定皮质脊髓神经元的作用的认识 活动模式，并告诉我们皮质和皮质下神经的身份和贡献 人口对皮质脊髓活动和运动的影响。

Abstract The ability to understand neural circuit mechanisms underlying behavior and motor control is critically dependent on our ability to modulate the activity of functional neural circuits reversibly, and with single cell precision. This project will causally test the predictions from Projects1-4 and in turn inform the models, data analyses and data collection in other Projects 2-4. For a clear understanding of the circuit mechanisms underlying motor control, cell-specific cortical and subcortical areas will be optogenetic manipulated through the use of closed-loop paradigms to directly assess the contributions of particular neural populations, or particular types of activity dynamics, on motor control. We will use 3 types of closed-loop operant paradigms: i) closed-loop paradigms where we optogenetically manipulate the activity of specific neuronal populations based on the behavioral state, ii) closed-loop paradigms where we optogenetically manipulate the activity of specific neuronal populations based on their activity, and iii) closed-loop paradigms where the neural activity will produce a specific behavioral outcome. We will test the contribution of cortical and subcortical areas to the activity of specific CSN populations and motor behavior by triggering the optogenetic manipulations on particular epochs of the behavior. We will also characterize the role of functionally identified neurons by using holographic optogenetic manipulations triggered by the neural activity patterns. Finally, we will use optical closed-loop operant brain-machine paradigms to investigate how upstream neural populations contribute to activity of corticospinal neurons versus non-corticospinal neurons in motor cortex. These experiments will test with multiple approaches the same hypotheses, and will permit us to causally establish causal connections between neural activity in different areas, and neural activity and behavior. They will provide unvaluable knowledge about the role of particular corticospinal neurons with specific projection patterns or with specific activity patterns, and also inform us about the identity and the contributions of cortical and subcortical neural populations to corticospinal activity, and to movement.