Corticospinal neurons in response control and movement coordination

皮质脊髓神经元在反应控制和运动协调中的作用

• 批准号: BB/Y004639/1
• 负责人: Ian Duguid
• 金额: $ 66.33万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY004639%2F1
• 关键词: Corticospinal; neurons; response; control; movement

To navigate through our ever-changing environment, we must continually process sensory information to make informed decisions and execute goal-oriented movements. This process of generating 'goal appropriate' actions whilst avoiding 'inappropriate' or unwanted actions is known as response control and is an essential component of everyday life necessary for our survival. Think of a fighter pilot on a low flying exercise through a mountainous area. The pilot uses all her available senses, visual flow, acoustic indicators, and proprioceptive feedback to ensure that she generates purposive voluntary movements of the control stick with the goal of selecting the appropriate flight path out of the mountains. All the while suppressing unwanted movements that would have significant and unwanted consequences. Central to the process of response control and movement coordination is an area of the brain known as the motor cortex which contains thousands of neurons (i.e., electrically excitable cells that convey information around the nervous system) that ultimately generate the 'command' signals that drive our muscles and help us move. Embedded within motor cortex are a particular type of output neuron named corticospinal neurons (CSNs) which send projections from the brain to the spinal cord to directly influence muscle activation. Despite decades of intensive investigation of the motor system, we still do not fully understand how thousands of CSNs organise their activity in time and space to generate efficient response control and coordination of our limbs during goal-directed movements. Previous work has shown that changes in the activity of single CSNs occur during the period when movement selection occurs, the so-called movement preparation phase, and throughout movement execution. Most CSNs show movement-related increased activity consistent with the generation of descending motor commands necessary for muscle activation. However, a significant proportion of CSNs display reduced activity during the same period, suggesting bidirectional changes in CSN output may be a prerequisite for efficient selection and execution of voluntary movements. These early correlative studies provided the first evidence that CSNs play an important role in motor control, but we lack a deeper understanding of how CSN activity is organised across motor cortex, how inputs to these neurons influence or shape their activity over time and how blocking of CSN output affects response control and movement coordination.To address this, we will train mice to perform an auditory cued motor task where the goal is to move a joystick to either a forward or backward reward zone (think of the fighter pilot analogy above) to receive a fluid reward. This goal-oriented task allows the exploration of both response control and movement coordination. We will use a combination of different brain recording techniques combined with approaches to manipulate the activity of neurons in real-time to try and understanding how dense populations of CSNs organise their activities during task execution and the importance of these patterns of activity for efficient task completion. Our findings will have important implications for understanding how CSNs execute appropriate movement of our limbs constituting an important step towards refining current theories of motor control.

为了应对不断变化的环境，我们必须不断处理感官信息，以做出明智的决策并执行以目标为导向的行动。这种产生“适合目标”的行动，同时避免“不适当”或不需要的行动的过程被称为反应控制，是我们生存所必需的日常生活的重要组成部分。想象一下战斗机飞行员在山区进行低空飞行演习。飞行员使用所有可用的感官、视觉流、声音指示器和本体感觉反馈来确保她有目的地随意移动控制杆，以选择离开山区的适当飞行路径。同时抑制会产生严重和不良后果的不必要的运动。反应控制和运动协调过程的核心是大脑中被称为运动皮层的区域，该区域包含数千个神经元（即在神经系统周围传递信息的可电兴奋细胞），最终产生驱动的“命令”信号我们的肌肉并帮助我们移动。嵌入运动皮层内的是一种特殊类型的输出神经元，称为皮质脊髓神经元（CSN），它将大脑的投射发送到脊髓，直接影响肌肉的激活。尽管对运动系统进行了数十年的深入研究，我们仍然不完全了解成千上万的 CSN 如何在时间和空间上组织它们的活动，以在目标导向的运动过程中对我们的四肢产生有效的反应控制和协调。先前的研究表明，单个CSN的活动变化发生在动作选择发生期间，即所谓的动作准备阶段，以及整个动作执行过程中。大多数 CSN 显示出与运动相关的活动增加，这与肌肉激活所需的下行运动命令的生成一致。然而，相当一部分 CSN 在同一时期表现出活动减少，这表明 CSN 输出的双向变化可能是有效选择和执行自主运动的先决条件。这些早期的相关研究提供了第一个证据，证明 CSN 在运动控制中发挥着重要作用，但我们缺乏对 CSN 活动如何在运动皮层中组织、这些神经元的输入如何随着时间的推移影响或塑造其活动以及如何阻断这些神经元的更深入的了解。 CSN 输出影响响应控制和运动协调。为了解决这个问题，我们将训练小鼠执行听觉提示运动任务，其目标是将操纵杆移动到向前或向后奖励区域（想想上面战斗机飞行员的类比）获得流动的奖励。这种以目标为导向的任务允许探索响应控制和运动协调。我们将结合使用不同的大脑记录技术和实时操纵神经元活动的方法，尝试了解密集的 CSN 群体在任务执行过程中如何组织其活动，以及这些活动模式对于高效完成任务的重要性。我们的研究结果对于理解 CSN 如何执行我们四肢的适当运动具有重要意义，这是完善当前运动控制理论的重要一步。