原肌球蛋白受体激酶B
长时程增强
神经科学
抗抑郁药
脑源性神经营养因子
突触后电位
突触可塑性
神经营养因子
生物
海马体
医学
受体
内科学
作者
Pei-Yi Lin,Z. Zack,Melissa Mahgoub,Ege T. Kavalali,Lisa M. Monteggia
出处
期刊:Cell Reports
[Elsevier]
日期:2021-08-01
卷期号:36 (7): 109513-109513
被引量:41
标识
DOI:10.1016/j.celrep.2021.109513
摘要
Ketamine produces rapid antidepressant action in patients with major depression or treatment-resistant depression. Studies have identified brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), as necessary for the antidepressant effects and underlying ketamine-induced synaptic potentiation in the hippocampus. Here, we delete BDNF or TrkB in presynaptic CA3 or postsynaptic CA1 regions of the Schaffer collateral pathway to investigate the rapid antidepressant action of ketamine. The deletion of Bdnf in CA3 or CA1 blocks the ketamine-induced synaptic potentiation. In contrast, ablation of TrkB only in postsynaptic CA1 eliminates the ketamine-induced synaptic potentiation. We confirm BDNF-TrkB signaling in CA1 is required for ketamine's rapid behavioral action. Moreover, ketamine application elicits dynamin1-dependent TrkB activation and downstream signaling to trigger rapid synaptic effects. Taken together, these data demonstrate a requirement for BDNF-TrkB signaling in CA1 neurons in ketamine-induced synaptic potentiation and identify a specific synaptic locus in eliciting ketamine's rapid antidepressant effects.
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