Ionic basis of neuronal hyperexcitability

神经元过度兴奋的离子基础

• 批准号: 7969519
• 负责人: JOHN CLAY
• 金额: $ 39.19万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7969519
• 关键词: Abdomen; Action Potentials; Aplysia; Axon; Back; Biological Models; Brain; Cell membrane; Cells; Complex; Deep Brain Stimulation; Disease; Drops; Electric Stimulation; Epilepsy; Exhibits; Feedback; Fire - disasters; Ganglia; Goals; Laboratories; Literature; Membrane; Membrane Potentials; Methodology; Methods; Modeling; Monitor; Myxoid cyst; Neurons; Pacemakers; Parkinson Disease; Periodicity; Physics; Preparation; Research; Signal Transduction; Squid; System; Techniques; Time; Work; base; indium arsenide; novel; novel strategies; sodium ion; systems research; theories; voltage; voltage clamp

Work during the current fiscal year has continued to focus on a control theory strategy from the physics literature for suppressing rhythmic firing in neurons. Pacemaker neurons have what is known as a "fixed point", usually close to -60 mV where the net membrane current is zero when the cell is held at that potential in voltage clamp conditions. Voltage clamp methodology is not relevant for suppressing excitability in the brain. We have suppressed excitability in the model preparations used in this laboratory (squid axons and Aplysia neurons) with a technique known as a dynamic clamp in which the voltage waveform is monitored in real time and a current signal proportional to the voltage is injected back into the cell with a delay. The reference point for the delay is the time of the maximum overshoot of the most recent action potential. When the delay is near the midpoint of the unperturbed pacemaker cycle and the feedback gain is at the appropriate level, firing stops immediately. The cell membrane potential is close to its fixed point and so the current injected by the feedback circuit immediately drops to zero, or close to zero. The membrane potential moves away from the fixed point since this point is unstable, but the feedback circuit applies current to keep it from moving more than a few mV away from that point. This is a novel mechanism for suppressing hyperexcitability in which very little current is required once firing has ceased. We are currently exploring the use of this methodology for other neuronal systems.

本财政年度的工作继续集中在物理学文献中的控制理论策略上，用于抑制神经元的节律性放电。 起搏神经元具有所谓的“固定点”，通常接近-60 mV，当细胞在电压钳条件下保持在该电位时，净膜电流为零。 电压钳方法与抑制大脑兴奋性无关。 我们已经抑制了兴奋性在本实验室中使用的模型制剂（鱿鱼轴突和神经元）的技术称为动态钳，其中电压波形被监测在真实的时间和电流信号成比例的电压被注入回细胞的延迟。 延迟的参考点是最近动作电位的最大过冲的时间。 当延迟接近未扰动起搏器周期的中点且反馈增益处于适当水平时，触发立即停止。 细胞膜电位接近其固定点，因此反馈电路注入的电流立即下降到零或接近零。 膜电位从固定点移开，因为该点是不稳定的，但是反馈电路施加电流以防止其从该点移开超过几mV。 这是一种新的机制，用于抑制过度兴奋，其中非常小的电流是需要一旦解雇已经停止。 我们目前正在探索将这种方法用于其他神经系统。