Insight into sensory-motor integration in genetically defined spinal interneurons

深入了解基因定义的脊髓中间神经元的感觉运动整合

• 批准号: RGPIN-2020-07078
• 负责人: Chopek, Jeremy
• 金额: $ 2.04万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763315
• 关键词: Insight; into; sensory; motor; integration

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.

运动行为涉及复杂的肌肉激活模式。这些自发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，这些神经网络在进行中的运动期间接收来自神经调节中心的下行输入和传入输入。随着可视化和操纵脊髓中特定神经元群体的遗传方法的进步，我们已经开始了解不同神经群体在产生运动行为中的作用。然而，这些方法通常涉及沉默或失活整个脊髓神经元群体，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滑和协调的运动活动所涉及的潜在连接的理解。我的研究计划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。拟议的研究将确定遗传定义的脊髓神经元在运动样活动期间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。为了实现这一目标，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质的应用的反应，在运动过程中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重要信息，并为我们目前关于脊髓网络如何产生运动和响应下行神经调节和传入输入的概念框架提供重要知识。