Nature特邀新闻与观点｜簇状放电为抑郁症创造了条件（中英文对照《自然》杂志邀请美国纽约西奈山医学院

北京时间2月15日凌晨2点，最新上线的《自然》杂志刊登了浙江大学医学院和求是高等研究院胡海岚团队的两篇研究长文（Research Article）。同一期的“

新闻与观点

”栏目，《自然》杂志邀请该领域的学者撰写文章，介绍这组研究的突破性进展及意义。文章指出：

两篇论文为抑郁症相关的大脑外侧缰核细胞簇状放电模式以及氯胺酮对这种放电方式的调节提供了关键的见解。

本文摘取其中关键内容，以中英文对照的方式与读者共享。

簇状放电为抑郁症创造了条件

Burst firing sets the stage for depression

作者：美国纽约西奈山医学院神经科学系 William M. Howe Paul J. Kenny

Salvos of neuronal activity in the brain’s lateral habenula, regulated by astrocyte cells, drive depression-like behaviours in rodents. The finding might help us to understand one antidepressant and to develop more.

在大脑外侧缰核中由星形胶质细胞调节的阵发型神经元活动促使啮齿类动物出现抑郁样行为。这一发现可能有助于我们理解一种抗抑郁药物的机制并开发更多。

Figure 1 | Burst firing in depression. a, The activation of membrane-spanning N-methyl-d-aspartate receptors (NMDARs) leads to an influx of calcium ions (Ca2+) that depolarizes neurons (the insides of which are negative relative to the outside in resting conditions), and causes firing. Ca2+ influx also leads to an efflux of potassium ions (K+) through K+-channel proteins. Yang et al. show that, in the brain’s lateral habenula (LHb), coordinated activity of NMDARs and T-type voltage-sensitive calcium channels (T-VSCCs) causes neuron firing to occur in a pattern of rapid bursts, and that such firing leads to depression-like symptoms in rats through unknown mechanisms. b, Cui et al.9 demonstrate that K+ ions are rapidly cleared away by nearby cells called astrocytes, which express K+ channels containing the protein Kir4.1. This facilitates rapid K+ efflux from the neuron and its entry into a state of hyperpolarization, which increases the likelihood of burst firing.

图1 |在抑郁症中的簇状放电。 a，跨膜N-甲基-d-天冬氨酸受体（NMDARs）的激活导致钙离子的内流，使神经元（其内部在静息条件下相对于外部为负）去极化与簇状放电。钙离子流入也导致钾离子通过钾离子通道流出。研究者显示，在大脑外侧缰核（LHb）中，NMDARs和T型电压依赖性钙通道（T-VSCCs）的协同活动导致神经元以快速爆发的模式发生簇状放电，并且这种放电通过未知的机制导致大鼠出现抑郁样症状。 b，在另一篇论文中，研究者证明钾离子被周围名为星形胶质细胞的细胞迅速清除，此类细胞表达含有蛋白质Kir4.1的钾离子通道。这有助于从神经元快速排出钾离子并进入超极化状态，从而增加簇状放电的可能性。

Together, these two papers provide crucial insights into a depression-associated pattern of cell firing in the LHb and its regulation by ketamine.

组合在一起，这两篇论文为抑郁症相关的大脑外侧缰核细胞簇状放电模式以及氯胺酮对这种放电方式的调节提供了关键的见解。

The current studies have several therapeu?tic implications. Previous studies link?ing astrocyte function to disease states have focused mostly on neurodegenerative and developmental disorders, but the current papers suggest that modulating the activity of these cells might be a way to treat psychiatric disorders.

raises the exciting possibility that T-VSCC blockers, or other compounds that suppress LHb burst firing, could be effec?tive antidepressants.

这两项研究对于抑郁症治疗方面的影响有几个方面。过往的研究将星形胶质细胞功能与疾病状态联系在起来主要集中在神经退行性疾病和发育障碍上，但是目前的研究表明调节这些细胞的活性可能是治疗精神类疾病的一种方法。

这两项研究提供了一个令人激动的可能性，即T-VSCC阻滞剂或抑制大脑外侧缰核簇状放电的其他化合物可能有潜力成为有效的抗抑郁药物。

This knowledge might facilitate the development of next-generation ketamine-related antidepres?sants that specifically target LHb activity and that might eliminate two major side effects of ketamine and other NMDAR blockers: their abuse potential and the induction of a transient, schizophrenia-like, psychotic state.

这些知识可能有助于开发下一代与氯胺酮相关的抗抑郁药，这些抗抑郁药将特异地针对大脑外侧缰核活性，有助于消除氯胺酮和其他NMDAR阻断剂的两种主要副作用：上瘾滥用可能性和诱发短暂精神分裂症状态。

原文链接：http://www.nature.com/articles/d41586-018-01588-z

本文内容来源：nature