Several brainstem nuclei degenerate in Parkinson's disease (PD). In addition to the well-characterized dopaminergic neurons of the substantia nigra pars compacta (SNc), the cholinergic neurons of the pedunculopontine nucleus (PPN) also degenerate in PD. One leading hypothesis of selective vulnerability is that pacemaking activity and the activation of low-threshold L-type calcium current are major contributors to tonic calcium load and cellular stress in SNc dopaminergic neurons. However, it is not yet clear whether the vulnerable PPN cholinergic neurons share this property. Therefore, we used two-photon dendritic calcium imaging and whole-cell electrophysiology to evaluate the role of L-type calcium channels in tonic and phasic dendritic calcium signals in PPN and SNc neurons. In addition, we investigated N- and P/Q-type calcium channel regulation of firing properties and dendritic calcium in PPN neurons. We found that blocking L-type channels reduces tonic firing rate and dendritic calcium levels in SNc neurons. By contrast, the tonic calcium load in PPN neurons did not depend on L-, N- or P/Q-type channels. However, we found that blocking either L-type (with nifedipine) or N- and P/Q-type (with omega-conotoxin MVIIC) channels reduces phasic calcium influx in PPN dendrites. Together, these findings show that L-type calcium channels play different roles in the activity of SNc and PPN neurons, and suggest that low-threshold L-type channels are not responsible for tonic calcium levels in PPN cholinergic neurons and are therefore not likely to be a source of selective vulnerability in these cells.

中文翻译：

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比较胆碱能脚桥神经元和多巴胺能黑质神经元的强直性和阶段性树突状钙

帕金森病 (PD) 中的几个脑干核会退化。除了特征明确的黑质致密部 (SNc) 多巴胺能神经元外，桥脚核 (PPN) 的胆碱能神经元也在 PD 中退化。选择性脆弱性的一个主要假设是，起搏活动和低阈值 L 型钙电流的激活是 SNc 多巴胺能神经元的强直钙负荷和细胞应激的主要贡献者。然而，尚不清楚易受攻击的 PPN 胆碱能神经元是否也具有这种特性。因此，我们使用双光子树突钙成像和全细胞电生理学来评估L型钙通道在PPN和SNc神经元的强直和阶段性树突钙信号中的作用。此外，我们还研究了 N 型和 P/Q 型钙通道对 PPN 神经元放电特性和树突状钙的调节。我们发现阻断 L 型通道会降低 SNc 神经元的强直放电率和树突钙水平。相比之下，PPN 神经元中的强直钙负荷不依赖于 L、N 或 P/Q 型通道。然而，我们发现阻断 L 型（使用硝苯地平）或 N 型和 P/Q 型（使用 omega-芋螺毒素 MVIIC）通道会减少 PPN 树突中的阶段性钙流入。总之，这些发现表明 L 型钙通道在 SNc 和 PPN 神经元的活动中发挥不同的作用，并表明低阈值 L 型通道不负责 PPN 胆碱能神经元的强直钙水平，因此不太可能是这些细胞选择性脆弱性的一个来源。