Insight into sensory-motor integration in genetically defined spinal interneurons

运动行为涉及肌肉激活的复杂模式。位于脊髓中的神经网络是这些运动运动的产生和模式所必需的。然而，为了确保顺畅和协调的运动活动，这些神经网络在进行中的运动中接受神经调制中心的下行输入和传入输入。随着可视化和操控脊髓中特定神经元群的遗传学方法的进步，我们已经开始了解不同的神经群在产生运动行为中所起的作用。然而，这些方法通常涉及沉默或使整个脊髓神经元群体失活，然后检查运动行为的表型或缺陷。为了补充这些方法，需要在蜂窝和本地网络层面进行基础调查，以增加我们对产生顺畅和协调的运动活动所涉及的潜在连接性的理解。我的研究重点是了解参与运动行为的“基因定义的”脊髓神经元的细胞和局部网络活动。这项拟议的研究将确定基因定义的脊髓神经元在运动样活动中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做出反应。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相结合的方法来研究在运动过程中和对分级传入刺激的反应中，各种神经调节剂的应用对细胞和网络的反应。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做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.