AMPA受体
氯胺酮
兴奋性突触后电位
神经传递
抗抑郁药
谷氨酸受体
药理学
神经科学
谷氨酸的
化学
突触后电位
NMDA受体
海马体
医学
受体
生物
抑制性突触后电位
生物化学
作者
Shi-Ge Xue,Jin-Gang He,Lingli Lu,Shiqian Song,Meimei Chen,Fang Wang,Jianguo Chen
标识
DOI:10.1038/s41467-023-42780-8
摘要
Ketamine produces rapid antidepressant effects at sub-anesthetic dosage through early and sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), however, the exact molecular mechanism still remains unclear. Transmembrane AMPAR regulatory protein-γ8 (TARP-γ8) is identified as one of AMPAR auxiliary subunits, which controls assemblies, surface trafficking and gating of AMPARs. Here, we show that ketamine rescues both depressive-like behaviors and the decreased AMPARs-mediated neurotransmission by recruitment of TARP-γ8 at the postsynaptic sites in the ventral hippocampus of stressed male mice. Furthermore, the rapid antidepressant effects of ketamine are abolished by selective blockade of TARP-γ8-containing AMPAR or uncoupling of TARP-γ8 from PSD-95. Overexpression of TARP-γ8 reverses chronic stress-induced depressive-like behaviors and attenuation of AMPARs-mediated neurotransmission. Conversely, knockdown of TARP-γ8 in excitatory neurons prevents the rapid antidepressant effects of ketamine.
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