Role of Active Synaptic Integration in Motoneuron Output

主动突触整合在运动神经元输出中的作用

• 批准号: 6895485
• 负责人: ROBERT H LEE
• 金额: $ 20.2万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895485
• 关键词: action potentials; cats; computer simulation; decerebration; electrophysiology; motor neurons; neural information processing; neural transmission; neurotransmitters; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): Motoneurons appear to have the ability to strongly amplify their own inputs based on neuromodulatory input from the brainstem. This amplification appears to preferentially effect fluctuating, rather than steady, synaptic input. In some input situations this effect results in what we refer to as "direct" mode firing. The objective of this project is to examine this amplification and to understand the role that a "fast" persistent inward current (PIC) plays in generating this amplification. The specific aims for this project are: 1) to quantify "fast" dendritic amplification of synaptic inputs; 2) to characterize direct mode firing; 3) to evaluate possible mechanisms for direct mode firing. In regards to the health relatedness of this project, this amplification may explain the profound weakness that occurs in cases of descending brainstem input disruption due to injury or disease. Overall, motoneuron research has been in a state of flux for several years as the effect of neuromodulators on motoneuron behavior has become increasingly apparent. The significance of this project is that it represents the culmination of this revolutionary period of change, bringing together much of the recent data along with the results anticipated from the work proposed here. In order to form this new view of motoneuron input processing based on steady inputs as well as input dynamics and neuromodulatory influences, the intended experimental approach utilizes a novel means of separating ionic currents based on their kinetics of activation. This approach permits instantaneous switching between measuring motoneuron firing and measuring ionic currents in intracellular in vivo experiments. Furthermore, voltage-clamp recording of currents generated by dynamic synaptic events can be examined for amplification and re-injected during current-clamp to determine their effect on the timing of individual spikes and firing rate in general.

描述(由申请人提供)：运动神经元似乎有能力根据来自脑干的神经调节输入强烈放大自己的输入。这种放大似乎优先影响波动的突触输入，而不是稳定的突触输入。在某些输入情况下，这种效应会导致我们所说的“直接”模式触发。该项目的目标是研究这种放大，并了解“快速”持续向内电流(PIC)在产生这种放大中所起的作用。这个项目的具体目标是：1)量化突触输入的“快速”树突放大；2)表征直接模式激发；3)评估直接模式激发的可能机制。关于这个项目的健康相关性，这种放大可能解释了由于受伤或疾病而导致脑干下行输入中断的情况下发生的严重弱点。总体而言，随着神经调节剂对运动神经元行为的影响日益明显，运动神经元的研究几年来一直处于不断变化的状态。这个项目的意义在于，它代表了这一革命性变革时期的顶峰，汇集了许多最近的数据以及这里提出的工作预期的结果。为了形成这种基于稳定输入以及输入动力学和神经调节影响的运动神经元输入处理的新观点，本实验方法利用了一种新的方法，基于离子电流的激活动力学来分离离子电流。这种方法允许在细胞内实验中在测量运动神经元放电和测量离子电流之间进行瞬时切换。此外，由动态突触事件产生的电流的电压钳记录可以被检查放大，并在电流钳期间重新注入，以确定它们对单个棘波的计时和一般的放电频率的影响。