Corticospinal neurons in response control and movement coordination

为了在不断变化的环境中导航，我们必须不断处理感官信息，以做出明智的决定并执行目标导向的运动。这种产生“目标适当”的行为，同时避免“不适当”或不想要的行为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。想象一下一个战斗机飞行员在山区低空飞行。飞行员使用所有可用的感官、视觉流、听觉指标和本体感受反馈，以确保她产生有目的的控制杆的自愿运动，目的是选择合适的飞行路线离开山区。一直在压制不必要的运动，这将产生重大和不必要的后果。反应控制和运动协调过程的中心是被称为运动皮层的大脑区域，其包含数千个神经元（即，神经系统中传递信息的电兴奋细胞），最终产生“命令”信号，驱动我们的肌肉，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），其将来自大脑的投射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，但我们仍然不完全了解成千上万的CSN如何在时间和空间上组织活动，以在目标导向的运动中产生有效的反应控制和肢体协调。以前的工作表明，在单一的CSN活动的变化发生在运动选择发生时，所谓的运动准备阶段，并在整个运动执行期间。大多数CSN显示与运动相关的活动增加，与肌肉激活所需的下行运动命令的产生一致。然而，在同一时期，CSN显示活动减少的显着比例，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CSN在运动控制中发挥重要作用的第一个证据，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CSN输出如何影响反应控制和运动协调的更深入了解。我们将训练小鼠执行听觉提示运动任务，目标是将操纵杆移动到向前或向后的奖励区（想想上面的战斗机飞行员类比）以获得流体奖励。这个目标导向的任务允许探索反应控制和运动协调。我们将使用不同的大脑记录技术与实时操纵神经元活动的方法相结合，以尝试了解密集的CSN群体在任务执行期间如何组织其活动，以及这些活动模式对有效完成任务的重要性。我们的研究结果将对理解CSNs如何执行我们的肢体适当的运动具有重要意义，这是完善当前运动控制理论的重要一步。

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.