Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.

Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.
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DOI:
10.1126/science.aax1522
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发表时间:
2019-10-11
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Diana MA
Diana MA
中科院分区:
其他
文献类型:
--
作者:
Otsu Y;Darcq E;Pietrajtis K;Mátyás F;Schwartz E;Bessaih T;Abi Gerges S;Rousseau CV;Grand T;Dieudonné S;Paoletti P;Acsády L;Agulhon C;Kieffer BL;Diana MA

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非常规的N-甲基-D-天冬氨酸(NMDA)受体亚基GluN 3 A/B在与另一个甘氨酸结合亚基GluN 1结合时可产生纯粹由甘氨酸激活的兴奋性电导。然而,尚未在天然成人组织中鉴定出功能性GluN 1/GluN 3受体。我们发现,GluN 1/GluN 3A受体在小鼠成年内侧缰(MHb),控制厌恶的生理状态的上丘脑区域的神经元中是可操作的。在没有甘氨酸能神经元专业化的MHb,神经胶质细胞通过GluN 1/GluN 3A受体调节神经元的活动。降低MHb中GluN 1/GluN 3A受体水平可防止位置厌恶条件反射。我们的研究通过证明甘氨酸通过兴奋性甘氨酸能NMDA受体控制负性情绪联想扩展了甘氨酸的生理和行为意义。甘氨酸NMDA受体的生理学
The unconventional N-methyl-D-aspartate (NMDA) receptor subunits GluN3A/B can generate excitatory conductances purely activated by glycine, when associated with the other glycine-binding subunit GluN1. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively-valued emotional associations via excitatory glycinergic NMDA receptors. Physiology of glycine NMDA receptors
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