Physiological significance of persistent inward currents in motor neurons

运动神经元持续内向电流的生理意义

• 批准号: 8502114
• 负责人: ANDREW J FUGLEVAND
• 金额: $ 12.64万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8502114
• 关键词: Action Potentials; Address; Amyotrophic Lateral Sclerosis; Animals; Behavior; Code; Computer Simulation; Development; Disease; Facies; Frequencies; Goals; Human; Isometric Contraction; Isometric Exercise; Knowledge; Lead; Measurement; Measures; Membrane; Methods; Motor; Motor Activity; Motor Neurons; Movement; Muscle; Muscle Contraction; Muscle Fibers; Nerve Tissue; Nervous system structure; Neurons; Output; Pattern; Physiological; Physiology; Preparation; Prevalence; Process; Property; Ramp; Recruitment Activity; Regulation; Reporting; Research Personnel; Role; Shapes; Signal Transduction; Skeletal Muscle; Source; Speed; Spinal cord injury; Staging; Stroke; Synapses; Testing; Time; Variant; Work; awake; base; human subject; indexing; insight; mind control; nervous system disorder; operation; prevent; public health relevance; relating to nervous system; response; simulation

DESCRIPTION (provided by applicant): Motor neurons receive synaptic inputs from many other neurons and convert these inputs into frequency-coded messages that are relayed to muscle fibers to cause contraction. It is often assumed that motor neurons generate spikes at rates in proportion to the excitatory synaptic input received. It is now recognized, however, that motor neurons have active processes, such as persistent inward currents (PICs) that may markedly modulate the relationship between synaptic input and firing rate output. PICs represent an intrinsic source of membrane depolarization that may lead to self-sustained firing of motor neurons, i.e., prolonged spiking in the absence of synaptic input. A number of ideas have been forwarded as to the functional significance of PICs, both in terms of the control of normal motor function and as an impaired process contributing to spasticity or amyotrophic lateral sclerosis (ALS). Yet, little is known about the actual physiological conditions under which PICs are activated. Recently, however, a method has been proposed to enable assessment of PIC activation in awake human subjects that involves quantifying an index referred to as ¿F from the activities of pairs of motor units recorded during voluntary contractions. The first specific aim of this project is to rigorously test the validity of the ¿F method based on insights gained from computer modeling. For this aim, we will measure ¿F for pairs of motor units during contractions that vary in rate of rise of force and duration in four muscles whose motor neurons are thought to possess differing capacities for generating PICs. The second specific aim will determine whether the initial high gain in motor unit firing rate observed during voluntary contraction is likely caused by PIC activation. For this aim, we will attempt to prevent activation of PICs altogether by artificially activating strong inhibitory inputs to motor neurons and determine whether this eliminates the initial steep rise in motor unit firing rate. Overall, this project is important because it will provide insight into the physiological conditions that activat PICs. Such information is crucial not only for understanding the fundamental operation of motor neurons but also for identifying the causes of neurological disorders such as spasticity and ALS.

描述（由申请人提供）：运动神经元接收来自许多其他神经元的突触输入，并将这些输入转换为频率编码消息，该消息被转发到肌肉纤维以引起收缩。人们通常认为运动神经元产生尖峰的速率与接收到的兴奋性突触输入成正比。然而，现在人们认识到运动神经元具有主动过程，例如持续内向电流（PIC），可以显着调节突触输入和放电率输出之间的关系。 PIC 代表膜去极化的内在来源，可能导致运动神经元自我持续放电，即在没有突触输入的情况下长时间放电。关于 PIC 的功能意义，人们提出了许多想法，无论是在正常运动功能的控制方面，还是作为导致痉挛或肌萎缩侧索硬化症 (ALS) 的受损过程方面。然而，人们对于其实际生理条件知之甚少。 PIC 已激活。然而，最近有人提出了一种方法来评估清醒人类受试者的 PIC 激活，该方法涉及根据随意收缩期间记录的成对运动单位的活动来量化称为 ¿F 的指数。该项目的第一个具体目标是根据计算机建模获得的见解严格测试 ¿F 方法的有效性。为此，我们将测量收缩期间运动单位对的 ¿F，这四块肌肉的力量上升速率和持续时间各不相同，这些肌肉的运动神经元被认为具有不同的产生 PIC 的能力。第二个具体目标将确定在随意收缩期间观察到的运动单位放电率的初始高增益是否可能是由 PIC 激活引起的。为此，我们将尝试阻止激活 通过人为激活运动神经元的强抑制输入来完全控制 PIC，并确定这是否消除了运动单元放电率的最初急剧上升。总的来说，这个项目很重要，因为它将提供对激活 PIC 的生理条件的深入了解。这些信息不仅对于理解运动神经元的基本运作至关重要，而且对于识别痉挛和 ALS 等神经系统疾病的原因也至关重要。