Ketamine blocks bursting in the lateral habenula to rapidly relieve depression
推荐理由
证明了氯胺酮通过阻断nmdar依赖性LHb神经元的爆发活动来解除下游单胺能奖励中心的抑制从而快速提升情绪，并为开发新的速效抗抑郁药提供了框架。
| 文章简介 | |
|---|---|
| 期刊 | NATURE |
| 发表年份 | 2018 |
| DOI | 10.1038/nature25509 |
| 类型 | 研究性工作 |
| 领域 | 抑郁症的病理机制 |
| 引用量 | 745 |
| 推荐信息 | |
|---|---|
| 推荐人 | 温小妍 |
| 审核 | 胡春华 |
| 推荐小组 | 抑郁小组 |
摘要
The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the ‘anti-reward center’, the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.
细分领域
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