Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs
Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs
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DOI：
10.1152/jn.00582.2001
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发表时间：
2002-03-01
影响因子：
2.5
通讯作者：
Wilson, CJ
中科院分区：
文献类型：
--
作者：
Bevan, MD;Magill, PJ;Wilson, CJ
通过相互连接的苍白球 (GP) 的 GABA 能抑制来调节丘脑底核 (STN) 的活动，在正常运动和运动障碍中发挥着重要作用。为了确定作用于 A 型受体的 GABA 能突触输入影响 STN 神经元放电的精确方式，我们记录了 STN 神经元对 GABA-A 抑制性突触后电位 (IPSP) 的反应，该电位是通过在 37 摄氏度的切片中使用穿孔贴片技术对内囊进行超最大电刺激而引起的。 GABA-A IPSP (EGABA-A IPSP) 的平均平衡电位为 -79.4 +/- 7.0 mV。单个 IPSP 破坏了 STN 神经元有节奏的单尖峰放电基础的自发振荡。随着 IPSP 幅度的增加，延长峰间间隔的有效性与诱发 IPSP 的振荡相位的相关性更强。因此，最大的 IPSP 倾向于重置振荡周期，而最小的 IPSP 倾向于在发射中产生相对与相位无关的延迟。在不同频率和不同时期诱发多个 IPSP，并研究了它们对处于不同极化水平的 STN 神经元的影响。多个IPSP减少和/或阻止动作电位的产生和/或产生足够的超极化以激活反弹去极化，从而产生单个尖峰或恢复有节奏的尖峰和/或产生突发活动。 IPSP 的模式和 STN 神经元的极化水平对于确定反应的性质至关重要。爆发的持续时间从 20 毫秒到几百毫秒不等，具体取决于突触后神经元的固有反弹特性。这些数据表明，来自 GP 的抑制输入可以在 STN 神经元中产生一系列放电模式，具体取决于 IPSP 的数量和频率以及突触后神经元的膜特性和电压。
The regulation of activity in the subthalamic nucleus (STN) by GABAergic inhibition from the reciprocally connected globus pallidus (GP) plays an important role in normal movement and disorders of movement. To determine the precise manner in which GABAergic synaptic input, acting at A-type receptors, influences the firing of STN neurons, we recorded the response of STN neurons to GABA-A inhibitory postsynaptic potentials (IPSPs) that were evoked by supramaximal electrical stimulation of the internal capsule using the perforated-patch technique in slices at 37degreesC. The mean equilibrium potential of the GABA-A IPSP (EGABA-A IPSP) was -79.4 +/- 7.0 mV. Single IPSPs disrupted the spontaneous oscillation that underlies rhythmic single-spike firing in STN neurons. As the magnitude of IPSPs increased, the effectiveness of prolonging the interspike interval was related more strongly to the phase of the oscillation at which the IPSP was evoked. Thus the largest IPSPs tended to reset the oscillatory cycle, whereas the smallest IPSPs tended to produce relatively phase-independent delays in firing. Multiple IPSPs were evoked at various frequencies and over different periods and their impact was studied on STN neurons held at different levels of polarization. Multiple IPSPs reduced and/or prevented action potential generation and/or produced sufficient hyperpolarization to activate a rebound depolarization, which generated a single spike or restored rhythmic spiking and/or generated a burst of activity. The pattern of IPSPs and the level of polarization of STN neurons were critical in determining the nature of the response. The duration of bursts varied from 20 ms to several hundred milliseconds, depending on the intrinsic rebound properties of the postsynaptic neuron. These data demonstrate that inhibitory input from the GP can produce a range of firing patterns in STN neurons, depending on the number and frequencies of IPSPs and the membrane properties and voltage of the postsynaptic neuron.