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性神经回路活动的能力， 精度这个项目将因果检验项目1 -4的预测，并反过来通知模型，数据 其他项目的分析和数据收集2-4.为了清楚地了解电路机制， 在潜在的运动控制中，细胞特异性皮质和皮质下区域将被光遗传学操纵， 使用闭环范例直接评估特定神经群体的贡献，或 特定类型的活动动力学，对运动控制。我们将使用3种类型的闭环操作范例： i）闭环范例，其中我们光遗传学地操纵特定神经元群体的活性 基于行为状态，ii）闭环范例，其中我们光遗传学地操纵 基于其活动的特定神经元群体，以及iii）闭环范例，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大脑皮层的作用。 特定CSN群体的活性和运动行为，通过触发光遗传学操纵， 行为的特定时期。我们还将通过使用功能识别的神经元来表征其作用。 由神经活动模式触发的全息光遗传学操纵。最后，我们将使用光学 闭环操作性脑机范例，以研究上游神经群体如何有助于 运动皮质中皮质脊髓神经元与非皮质脊髓神经元的活动。这些实验将测试 用多种方法来验证相同的假设，并将允许我们建立因果关系 不同区域的神经活动，以及神经活动和行为之间的关系。他们将提供毫无价值的 关于特定皮质脊髓神经元的作用的知识，具有特定的投射模式或具有特定的 活动模式，并告知我们有关的身份和贡献，皮层和皮层下的神经 人群皮质脊髓活动和运动。

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.