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

基本信息

批准号：
9015482
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
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-15 至 2017-12-31
项目状态：
已结题

项目摘要

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（由适用提供）：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的消息，这些消息传递到肌肉纤维会导致收缩。通常假定运动神经元与接收到的兴奋性突触输入成正比产生峰值。但是，现在已经认识到，运动神经元具有主动过程，例如持续的内向电流（图片），这些过程可能会显着调节合成输入和发射速率输出之间的关系。图片代表了膜沉积的内在来源，可能导致运动神经元的自我维持的发射，即在没有合成输入的情况下长时间的尖峰。关于图片的功能意义，已经转发了许多想法，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性侧向硬化症（ALS）的过程受损的过程。然而，关于实际生理状况知之甚少图片被激活。然而，最近，已经提出了一种方法来评估醒着人类受试者中的PIC激活，该方法涉及量化从自愿收缩期间记录的运动单元的活动中称为f的指数。该项目的第一个具体目的是严格测试基于从计算机建模中获得的见解的'F方法的有效性。为此，我们将在收缩期间测量成对的运动单位的f，而四个肌肉的力和持续时间的增加，其运动神经元被认为具有产生图片的能力不同。第二个特定目标将确定在自愿收缩期间观察到的电动机发射速率的初始高增益可能是由PIC激活引起的。为此，我们将试图防止激活通过人为激活运动神经元的强抑制性输入，完全激活了图片的图片，并确定这是否消除了运动单位发射速率的初始钢提升。总体而言，该项目很重要，因为它将洞悉Activat Pics的物理状况。这些信息不仅对于理解运动神经元的基本操作至关重要，而且对于确定神经系统疾病（如痉挛和ALS）的原因。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations.

甘氨酸受体突变小鼠运动神经元的内在和突触稳态可塑性。

DOI：
10.1152/jn.00728.2013
发表时间：
2014
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Tadros,MA;Farrell,KE;Schofield,PR;Brichta,AM;Graham,BA;Fuglevand,AJ;Callister,RJ
通讯作者：
Callister,RJ

Inhibition linearizes firing rate responses in human motor units: implications for the role of persistent inward currents.

抑制使人类运动单位的放电率反应线性化：对持续内向电流作用的影响。