Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Eur J Neurosci. 2011 Aug;34(3):404-15. doi: 10.1111/j.1460-9568.2011.07766.x. Epub 2011 Jul 4.
The pedunculopontine nucleus (PPN), part of the reticular activating system, modulates waking and paradoxical sleep. During waking and paradoxical sleep, EEG responses are characterized by low-amplitude, high-frequency oscillatory activity in the beta-gamma band range (~20-80 Hz). We have previously reported that gamma band activity may be intrinsically generated by the membrane electroresponsiveness of PPN neurons, and that the neuronal ensemble generates different patterns of gamma activity in response to specific transmitters. This study attempted to identify the voltage-gated calcium and potassium channels involved in the rising and falling phases of gamma oscillations in PPN neurons. We found that all rat (8-14 day) PPN cell types showed gamma oscillations in the presence of TTX and synaptic blockers when membrane potential was depolarized using current ramps. PPN neurons showed gamma oscillations when voltage-clamped at holding potentials above -30 mV, suggesting that their origin may be spatially located beyond voltage-clamp control. The average frequency for all PPN cell types was 23 ± 1 Hz and this increased under carbachol (47 ± 2 Hz; anova df = 64, t = 12.5, P < 0.001). The N-type calcium channel blocker ω-conotoxin-GVIA partially reduced gamma oscillations, while the P/Q-type blocker ω-agatoxin-IVA abolished them. Both ω-CgTX and ω-Aga blocked voltage-dependent calcium currents, by 56 and 52% respectively. The delayed rectifier-like potassium channel blocker α-dendrotoxin also abolished gamma oscillations. In carbachol-induced PPN population responses, ω-agatoxin-IVA reduced higher, and ω-CgTx mostly lower, frequencies. These results suggest that voltage-dependent P/Q- and, to a lesser extent, N-type calcium channels mediate gamma oscillations in PPN.
脑桥被盖核（PPN），网状激活系统的一部分，调节觉醒和异相睡眠。在觉醒和异相睡眠期间，脑电图反应的特征是在β-γ频段（~20-80 Hz）具有低幅度、高频率的振荡活动。我们之前报道过，γ 频段活动可能是由 PPN 神经元的膜电反应性内在产生的，神经元集合根据特定的递质产生不同的γ 活动模式。本研究试图确定参与 PPN 神经元γ 振荡上升和下降相的电压门控钙和钾通道。我们发现，当使用电流斜坡使膜电位去极化时，所有大鼠（8-14 天）PPN 细胞类型在 TTX 和突触阻断剂存在的情况下均显示出 γ 振荡。当电压钳制在保持电位高于-30 mV 时，PPN 神经元显示出 γ 振荡，这表明其起源可能位于电压钳制控制之外的空间位置。所有 PPN 细胞类型的平均频率为 23±1 Hz，在乙酰胆碱作用下增加到 47±2 Hz（anova df = 64，t = 12.5，P < 0.001）。N 型钙通道阻滞剂 ω-芋螺毒素-GVIA 部分减少了 γ 振荡，而 P/Q 型阻滞剂 ω-海葵毒素-IVA 则完全消除了它们。两种 ω-CgTX 和 ω-Aga 均阻断电压依赖性钙电流，分别为 56%和 52%。延迟整流样钾通道阻滞剂 α-树突毒素也消除了 γ 振荡。在乙酰胆碱诱导的 PPN 群体反应中，ω-海葵毒素-IVA 降低了较高的频率，而 ω-CgTX 主要降低了较低的频率。这些结果表明，电压依赖性 P/Q-，并且在较小程度上，N 型钙通道介导 PPN 中的 γ 振荡。
