Fujita Tomohiro, Fukai Tomoki, Kitano Katsunori
Graduate School of Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
J Comput Neurosci. 2012 Jun;32(3):539-53. doi: 10.1007/s10827-011-0368-2. Epub 2011 Oct 13.
The activity patterns of the globus pallidus (GPe) and subthalamic nucleus (STN) are closely associated with motor function and dysfunction in the basal ganglia. In the pathological state caused by dopamine depletion, the STN-GPe network exhibits rhythmic synchronous activity accompanied by rebound bursts in the STN. Therefore, the mechanism of activity transition is a key to understand basal ganglia functions. As synchronization in GPe neurons could induce pathological STN rebound bursts, it is important to study how synchrony is generated in the GPe. To clarify this issue, we applied the phase-reduction technique to a conductance-based GPe neuronal model in order to derive the phase response curve (PRC) and interaction function between coupled GPe neurons. Using the PRC and interaction function, we studied how the steady-state activity of the GPe network depends on intrinsic membrane properties, varying ionic conductances on the membrane. We noted that a change in persistent sodium current, fast delayed rectifier Kv3 potassium current, M-type potassium current and small conductance calcium-dependent potassium current influenced the PRC shape and the steady state. The effect of those currents on the PRC shape could be attributed to extension of the firing period and reduction of the phase response immediately after an action potential. In particular, the slow potassium current arising from the M-type potassium and the SK current was responsible for the reduction of the phase response. These results suggest that the membrane property modulation controls synchronization/asynchronization in the GPe and the pathological pattern of STN-GPe activity.
苍白球(GPe)和底丘脑核(STN)的活动模式与基底神经节的运动功能及功能障碍密切相关。在多巴胺耗竭引起的病理状态下,STN-GPe网络呈现节律性同步活动,并伴有STN中的反弹爆发。因此,活动转换机制是理解基底神经节功能的关键。由于GPe神经元的同步化可诱发病理性STN反弹爆发,研究GPe中同步化如何产生很重要。为阐明这一问题,我们将相位还原技术应用于基于电导的GPe神经元模型,以推导相位响应曲线(PRC)和耦合GPe神经元之间的相互作用函数。利用PRC和相互作用函数,我们研究了GPe网络的稳态活动如何依赖于内在膜特性,即改变膜上的离子电导。我们注意到,持续性钠电流、快速延迟整流Kv3钾电流、M型钾电流和小电导钙依赖性钾电流的变化会影响PRC形状和稳态。这些电流对PRC形状的影响可归因于动作电位后放电期的延长和相位响应的降低。特别是,由M型钾电流和SK电流产生的缓慢钾电流是相位响应降低的原因。这些结果表明,膜特性调节控制着GPe中的同步化/去同步化以及STN-GPe活动的病理模式。