Mechanisms underlying spontaneous oscillation and rhythmic firing in rat subthalamic neurons
Mechanisms underlying spontaneous oscillation and rhythmic firing in rat subthalamic neurons
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DOI：
10.1523/jneurosci.19-17-07617.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Wilson, CJ
中科院分区：
文献类型：
--
作者：
Bevan, MD;Wilson, CJ
丘脑底神经元驱动静息动物的基底神经节输出神经元，并在运动期间将皮质和丘脑活动传递给相同的输出神经元。本研究的第一个目的是确定底丘脑神经元在体外自发活动的机制，并深入了解其在体内的静息放电。第二个目标是确定底丘脑神经元的反应去极化电流injection和如何内在的属性可能会塑造他们的反应，皮层和丘脑的输入在movement. Cell贴附和全细胞记录从底丘脑神经元的脑切片制备3至4周龄的大鼠。丘脑底核神经元的缓慢、有节奏的放电对兴奋性突触传递的阻断有抵抗力，这表明其自发放电的基础是内在电流。一个持续的钠电流是在振荡的去极化阶段的电流源。一个强大的后超极化后，每个动作电位足以终止去极化。一个长时间的组成部分的尖峰后超极化确定的振荡周期，并产生一个apamin敏感的钙激活钾电流。负责该电流的钙离子内流与动作电位相关。丘脑底核神经元表现出S形频率-电流关系，其中较陡的部分开始于类似于30-40 Hz。这种特性使得丘脑底核神经元在运动时对高放电率的输入比在休息时对低放电率的输入更敏感。我们认为阈下持续性钠电流克服了钙激活钾电流，后者在高频放电过程中积累，是对>30 Hz电流敏感性增强的基础。
Subthalamic neurons drive basal ganglia output neurons in resting animals and relay cortical and thalamic activity to the same output neurons during movement. The first objective of this study was to determine the mechanisms underlying the spontaneous activity of subthalamic neurons in vitro and to gain insight into their resting discharge in vivo. The second objective was to determine the response of subthalamic neurons to depolarizing current injection and how intrinsic properties may shape their response to cortical and thalamic inputs during movement.Cell-attached and whole-cell recordings were made from subthalamic neurons in brain slices prepared from 3- to 4-week-old rats. The slow, rhythmic discharge of subthalamic neurons was resistant to blockade of excitatory synaptic transmission indicating that intrinsic currents underlie their spontaneous discharge. A persistent sodium current was the source of current during the depolarizing phase of the oscillation. A powerful afterhyperpolarization following each action potential was sufficient to terminate the depolarization. A long duration component of the spike afterhyperpolarization determined the period of the oscillation and was generated by an apamin-sensitive calcium-activated potassium current. Calcium entry responsible for that current was associated with action potentials.Subthalamic neurons exhibited a sigmoidal frequency-current relationship with the steeper portion starting at similar to 30-40 Hz. This property makes subthalamic neurons more sensitive to input at high firing rates associated with movement than at low rates associated with rest. We propose that the subthreshold persistent sodium current overcomes calcium activated potassium current which accumulates during high frequency firing and underlies the enhanced sensitivity to current >30 Hz.