Control properties of single motor units

背景运动神经元是连接中枢神经系统和肌肉的唯一纽带，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。运动神经元的放电由调节传统突触兴奋和抑制的“电离性”机制和调节持续内向电流(PIC)并控制细胞对突触输入的反应方式的“代谢性”机制控制。PIC是由单胺控制的，这些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，单胺类物质在多大程度上调节人类运动神经元的放电尚不清楚。拟议的实验将使用一种新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，以覆盖脊髓中一系列单胺水平。目的1.建立运动神经元兴奋性在设计的条件下变化的范围，该范围包括广泛水平的单胺能驱动至脊髓。2.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。在记录运动单位的同时，将对神经和肌肉施加低电流刺激，这些肌肉可以弯曲和伸展脚踝和手腕。表面肌电信号也将被记录。数据将在以下条件下收集，按预测单胺能驱动从最低到最高的顺序排列：1.睡眠。在快速眼动睡眠期间，单胺类药物的驱动力最低。此前，我们已经成功地在三名睡眠受试者中以比目前使用的更高的强度进行了刺激。2.“完全放松”。受试者将被要求“完全”放松，这是一种终止非自愿运动单位放电的条件，这是PIC激活的一个标志，持续时间长于刺激。3.清醒放松(对照)。受试者将被要求正常坐着。这是这些实验的“控制”条件，旨在接近“中等”的单胺能驱动。4.收缩后。低电流刺激将在受试者进行5次短暂的自愿收缩后立即给予。这项任务是为了给运动神经元中的图片“预热”，增加它们对运动神经元发射的贡献。5.最大收缩后自主收缩。受试者将进行最大限度的收缩，以进一步热身运动神经元，并增加单胺能驱动。6.后咖啡因。参与者将摄入咖啡因，这是一种腺苷受体激动剂，可以增加单胺类水平。这些实验将在资助期的前三年进行。电刺激和自发产生不同幅度的TA收缩，以评估相互抑制对臂部和腿部运动池PIC的影响。对30名S的刺激将以低于运动阈值的强度传递到引起10%MVC收缩的强度。自愿激活的范围将从宽松到10%的MVC。这些实验将在资助期的最后两年内完成。意义这些实验将提供有关PIC在多大程度上促进人类运动神经元放电的新信息。目前，关于电离机制在不同条件下如何控制运动神经元单位放电的了解很多，本实验将扩展这一理解，为运动神经元代谢性控制中的任务依赖性变化提供新的信息。

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.