Comparing tonic and phasic calcium in the dendrites of vulnerable midbrain neurons.
Comparing tonic and phasic calcium in the dendrites of vulnerable midbrain neurons.
复制标题
比较脆弱中脑神经元树突中的强直性和阶段性钙。
DOI：
10.1101/2023.08.28.555184
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Evans,RebekahC
中科院分区：
文献类型：
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作者：
Chen,RitaYu-Tzu;Evans,RebekahC
帕金森病（Parkinson's Disease，PD）患者中脑多个核团变性。这些核团中的许多都具有共同的特征，这些特征被认为有助于它们的选择性脆弱性，包括起搏活动和高水平的钙内流。PD时，除了黑质腹侧部（SNc）的多巴胺能神经元外，脚桥核（PPN）的胆碱能神经元也退化。已经确定，低阈值L型钙电流是SNc多巴胺能神经元中强直性钙的主要贡献者，并假设有助于其选择性脆弱性。然而，目前尚不清楚是否脆弱的PPN胆碱能神经元共享这一属性。因此，我们使用双光子树突状钙成像和全细胞电生理学来评估L型钙通道在PPN神经元的紧张性和阶段性活动中的作用以及相应的树突状钙信号，并直接将这些特征与SNc神经元进行比较。我们发现，阻断L-型通道可降低SNc神经元的紧张性放电率和树突钙水平。相比之下，起搏过程中PPN神经元的钙负荷不依赖于L型通道。然而，我们发现阻断L-型通道减少PPN树突中的阶段性钙内流。总之，这些研究结果表明，L型钙通道在SNc和PPN神经元的活性中发挥不同的作用，并表明低阈值L型通道不负责PPN胆碱能神经元中的强直性钙水平，因此不太可能成为这些细胞中选择性脆弱性的来源。
Several midbrain nuclei degenerate in Parkinson’s Disease (PD). Many of these nuclei share the common characteristics that are thought to contribute to their selective vulnerability, including pacemaking activity and high levels of calcium influx. 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. It is well established that the low-threshold L-type calcium current is a main contributor to tonic calcium in SNc dopaminergic neurons and is hypothesized to contribute to their selective vulnerability. 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 the tonic and phasic activity of PPN neurons and the corresponding dendritic calcium signal and directly compare these characteristics to SNc neurons. We found that blocking L-type channels reduces tonic firing rate and dendritic calcium levels in SNc neurons. By contrast, the calcium load in PPN neurons during pacemaking did not depend on L-type channels. However, we find that blocking L-type 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.