Control properties of single motor units

*运动神经元是中枢神经系统和肌肉之间的唯一联系，了解它们如何将突触输入转化为运动输出是理解运动控制的基础。运动神经元放电受“离子化”机制和“代谢”机制控制，前者介导传统的突触兴奋和抑制，后者调节持续向内电流（PICs）并控制细胞对突触输入的反应方式。PICs是由单胺控制的，单胺从脑干释放到整个脊髓。单胺被认为为手头的任务设定了脊髓兴奋性的背景水平。然而，单胺调节人类运动神经元放电的程度尚不清楚。该实验将采用一种新颖的低电流电刺激技术来推断在选定的条件下，PIC对运动神经元放电的贡献，这些条件涵盖了脊髓中单胺的一系列水平。建立运动神经元兴奋性在设计条件下变化的范围，以涵盖广泛的单胺能驱动到脊髓的水平。确定抑制输入可用于控制特定运动池的运动神经元兴奋性的程度。**方案*低电流刺激将应用于神经和肌肉弯曲和伸展脚踝和手腕，同时记录运动单位。表面肌电图也将被记录。数据将在以下条件下收集，这些条件按照单胺能驱动预测从低到高的顺序排列：睡眠。快速眼动睡眠时单胺驱力最低。在此之前，我们已经成功地在三个睡眠对象身上施加了比现在更高强度的刺激。* 2。“完全放松。”受试者将被要求“完全”放松，这种情况将终止非自愿运动单元放电，这是PIC激活的标志，持续时间超过刺激。清醒，放松（控制）。受试者将被要求正常坐下。这是这些实验的“控制”条件，旨在近似于“介质”单胺驱动。Post-contraction。在受试者进行5次短暂的自愿收缩后，立即给予低电流刺激。这项任务旨在“预热”运动神经元中的PICs，并增加它们对运动神经元放电的贡献。最大收缩后自愿收缩。受试者将进行最大收缩以进一步热身运动神经元并增加单胺能驱动。Post-caffeine。参与者将注射咖啡因，一种增加单胺能水平的腺苷受体激动剂。*这些实验将在资助期的头三年进行。*会自动产生不同的TA收缩幅度，以评估相互抑制对手臂和腿部运动池中PICs的影响。刺激将在低于运动阈值的强度下持续30秒，从而引起10%的MVC收缩。自愿激活的范围在松弛和10%MVC之间。这些实验将在资助期的最后两年完成。**意义*这些实验将为PICs在多大程度上促进人类运动神经元放电提供新的信息。目前，关于各电离性机制在不同条件下如何控制电机单元放电的研究尚不清楚；目前的实验将扩展这一认识，以提供关于运动神经元代谢控制的任务依赖性变化的新信息。

Background * Motoneurons provide the only link between the central nervous system and muscle and understanding how they transform synaptic input into motor output is fundamental to understanding the control of movement. Motoneuron discharge is controlled by "ionotropic" mechanisms that mediate traditional synaptic excitation and inhibition and "metabotropic" mechanisms that regulate persistent inward currents (PICs) and control the way the cell responds to synaptic inputs. PICs are controlled by monoamines that are released throughout the spinal cord from the brainstem. Monoamines are thought to set a background level of spinal excitability for the task at hand. However, the extent to which monoamines regulate motoneuron discharge in humans is unclear. The proposed experiments will employ a novel low-current electrical stimulation technique to infer the PIC contribution to motoneuron discharge during conditions selected to cover a range of levels of monoamines in the spinal cord.**Objectives*1. Establish the range over which motoneuronal excitability varies during conditions designed to encompass a wide range of levels of monoaminergic drive to the spinal cord.*2. Establish the extent to which inhibitory inputs can be used to control motoneuronal excitability of specific motor pools. **Protocol*Low-current stimulation will be applied to the nerves to the muscles that flex and extend the ankle and wrist while motor units are recorded. Surface electromyography will also be recorded. Data will be collected under the following conditions that are presented in order of lowest to highest predicted monoaminergic drive:*1. Sleep. Monoamine drive is lowest during rapid eye movement sleep. Previously, we have delivered stimulation successfully in three sleeping subjects at higher intensities than will be used presently. *2. Relax "completely." Subjects will be asked to relax "completely," a condition that terminates involuntary motor unit discharge, a hallmark of PIC activation, that outlasts the stimulation.*3. Awake relaxed (control). Subjects will be requested to sit normally. This is the "control" condition for these experiments and is intended to approximate the "medium" monoaminergic drive.*4. Post-contraction. Low current stimulation will be delivered immediately after subjects perform 5 brief voluntary contractions. This task is intended to "warm up" the PICs in motoneurons and increase their contribution to motoneuron firing.*5. Post-maximum voluntary contraction. Subjects will perform a maximum contraction to further warm-up motoneurons and increase monoaminergic drive.*6. Post-caffeine. Participants will injest caffeine, an adenosine receptor agonist that increases monoaminergic levels.*These experiments will be conducted over the first three years of the funding period. *Different amplitudes of contractions of TA will be generated electrically and voluntarily to assess the effect of reciprocal inhibition on PICs in motor pools in the arms and legs. The stimulation will be delivered for 30 s at intensities below motor threshold to that which evokes a contraction of 10% MVC. Voluntary activation will range between relaxed and 10%MVC. These experiments will be completed over the final two years of the funding period. **Significance*These experiments will provide new information about the extent to which PICs contribute to motoneuron discharge in humans. Currently, much is known about how ionotropic mechanisms control motor unit discharge under different conditions; the present experiments will extend this understanding to provide novel information about task-dependent changes in metabotropic control of motoneurons.