Control properties of single motor units

背景 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。运动神经元放电由介导传统突触兴奋和抑制的“离子型”机制和调节持续内向电流（PIC）并控制细胞对突触输入的响应方式的“代谢型”机制控制。PIC由从脑干释放到整个脊髓的单胺控制。单胺被认为是为手头的任务设定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。拟议的实验将采用一种新的低电流电刺激技术来推断PIC的贡献，运动神经元放电的条件下选择的范围内的单胺在脊髓中。 目标 1.建立运动神经元兴奋性变化的范围，在设计的条件下，包括范围广泛的单胺能驱动到脊髓。 2.确定抑制性输入在多大程度上可用于控制特定运动池的运动神经元兴奋性。 议定书 低电流刺激将被施加到神经到肌肉，弯曲和伸展脚踝和手腕，同时记录运动单位。还将记录表面肌电图。将在以下条件下收集数据，按预测单胺能驱力从低到高的顺序列出： 1.睡吧单胺驱动在快速眼动睡眠期间最低。以前，我们已经成功地提供了刺激在三个睡眠科目在更高的强度比目前将使用。 2.完全放松。受试者将被要求“完全”放松，这是一种终止不自主运动单位放电的条件，这是PIC激活的标志，持续时间超过刺激。 3.清醒放松（控制）。要求受试者正常坐位。这是这些实验的“对照”条件，旨在接近“中等”单胺能驱动。 4.宫缩后期。在受试者进行5次短暂自主收缩后，将立即输送低电流刺激。这项任务旨在“热身”运动神经元中的PIC，并增加它们对运动神经元放电的贡献。 5.最大自主收缩后。受试者将进行最大收缩，以进一步预热运动神经元并增加单胺能驱动。 6.后咖啡因。参与者将注射咖啡因，一种腺苷受体激动剂，增加单胺能水平。 这些试验将在供资期的头三年进行。 将通过电和自主产生不同幅度的TA收缩，以评估相互抑制对手臂和腿部运动池中PIC的影响。刺激将以低于运动阈值的强度输送30 s，以引起10%MVC的收缩。自主激活的范围介于放松和10%MVC之间。这些实验将在供资期的最后两年完成。 意义 这些实验将提供有关PIC对人类运动神经元放电的贡献程度的新信息。目前，很多是已知的离子型机制如何控制电机单位放电在不同的条件下，本实验将扩展这种理解，提供新的信息，任务依赖性的变化，代谢控制的运动神经元。

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.