Insight into sensory-motor integration in genetically defined spinal interneurons

运动行为涉及复杂的肌肉激活模式。这些运动的产生和模式需要位于脊髓中的神经网络。然而，为了确保平稳和协调的运动活动，这些神经网络在正在进行的运动中接受来自神经调节中心的下行输入和传入输入。随着遗传方法的进步，我们可以可视化和操纵脊髓中特定的神经元群，我们已经开始了解不同的神经群在产生运动行为中的作用。然而，这些方法通常涉及沉默或使整个脊髓神经元群失活，然后检查运动行为的表型或缺陷。为了补充这些方法，需要在细胞和局部网络水平上进行基础研究，以增加我们对产生平稳和协调的运动活动所涉及的潜在连通性的理解。我的研究项目侧重于了解参与运动行为的“遗传定义”脊髓神经元的细胞和局部网络活动。拟议的研究将确定运动样活动期间遗传定义的脊髓神经元的细胞和网络活动模式，以及这些神经元如何对神经调节和传入刺激作出反应。为了实现这一点，在转基因小鼠模型中，我将使用体外全细胞贴片电生理学和钙成像的组合来研究细胞和网络对各种神经调节剂的应用的反应，在运动期间和对分级传入刺激的反应。这些研究将为理解参与运动活动的脊髓神经元的细胞反应提供必要的信息，并为我们目前关于脊髓网络如何产生运动并对下行神经调节和传入输入作出反应的概念框架提供重要的知识。

Locomotor behaviour involves a complex pattern of muscle activation. Neural networks located in spinal cord are required for the generation and pattern of these locomotor movements. However, to ensure smooth and coordinated locomotor activity, these neural networks receive descending input from neuromodulatory centres and afferent input during on-going locomotion. With the advancement of genetic approaches to visualize and manipulate specific neuronal population in the spinal cord, we have begun to understand the roles that distinct neural populations have in producing locomotor behaviours. However, these approaches typically involve silencing or inactivating an entire population of spinal neurons and then examining for a phenotype or deficit in locomotor behaviours. To complement these approaches, fundamental investigations at the cellular and local network level are needed to increase our understanding of the underlying connectivity involved in producing smooth and coordinated locomotor activity. My research program focuses on understanding the cellular and local network activity of "genetically defined" spinal neurons involved in locomotor behaviours. The proposed research will determine the cellular and network activity patterns of genetic defined spinal neurons during locomotor-like activity, and how these neurons respond to neuromodulation and afferent stimulation. To achieve this, in transgenic mouse models, I will use a combination of in-vitro whole cell-patch electrophysiology and calcium imaging to investigate both the cellular and networks responses to application of various neuromodulators, during locomotion and in response to graded afferent stimulation. These studies will provide essential information in understanding the cellular responses of spinal neuron involved in locomotor activity and provide important knowledge regarding our current conceptual framework of how spinal networks produce locomotion and respond to descending neuromodulation and afferent inputs.