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.

为了浏览我们不断变化的环境，我们必须不断处理感官信息以做出明智的决策并执行面向目标的动作。在避免“不适当”或不必要的动作的同时，产生“适当”行动的过程被称为响应控制，是我们生存所必需的日常生活的重要组成部分。想想通过山区的低空锻炼中的战斗机飞行员。飞行员使用她所有可用的感官，视觉流，声学指示器和本体感受反馈，以确保她生成控制棒的有目的的自愿运动，以便选择从山上选择适当的飞行路径。一直抑制不必要的运动，这些运动将带来重大和不必要的后果。响应控制和运动配位过程的核心是大脑的一个区域，称为运动皮层，其中包含数千个神经元（即传达神经系统围绕信息的电细胞），最终会产生“命令”信号，这些信号驱动我们的肌肉并帮助我们移动。嵌入运动皮质中的嵌入是一种特定类型的输出神经元，称为皮质脊髓神经元（CSN），该神经元将大脑的投影发送到脊髓，以直接影响肌肉激活。尽管对运动系统进行了数十年的深入研究，但我们仍然并不完全了解成千上万的CSN在时间和空间上如何组织其活动，以在目标指导的运动中产生有效的响应控制和四肢协调。先前的工作表明，单个CSN活动的变化发生在运动选择，所谓的运动制备阶段以及整个运动执行期间。大多数CSN表现出与运动相关的增加活动，这与肌肉激活所必需的下降运动命令的产生一致。但是，在同一时期，很大一部分的CSN表现出减少的活性，这表明CSN输出的双向变化可能是有效选择和执行自愿运动的先决条件。这些早期的相关研究提供了第一个证据，表明CSN在运动控制中起着重要的作用，但是我们对CSN活动如何在整个运动皮质中组织组织，对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CSN输出的阻断如何影响响​​应响应和运动的配置。 （想想上面的战斗机飞行员类比）获得流畅的奖励。这项面向目标的任务允许探索响应控制和运动协调。我们将结合不同的大脑记录技术与操纵神经元实时操纵活动的方法的组合，以尝试并了解CSN的密集人群如何在任务执行过程中组织其活动以及这些活动模式对于有效的任务完成的重要性。我们的发现将对理解CSN如何执行四肢的适当运动具有重要意义，这是迈向精炼当前运动控制理论的重要一步。