甘氨酸门控 GluN1/GluN3A NMDA 受体在成年内侧缰核中控制厌恶反应。
Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.
机构信息
Institut de Biologie de l'École Normale Supérieure (IBENS), INSERM U1024, CNRS UMR8197, École Normale Supérieure, Université PSL, 75005 Paris, France.
Department of Psychiatry, School of Medicine, Douglas Hospital Research Center, McGill University, Montreal, QC H4H 1R3, Canada.
出版信息
Science. 2019 Oct 11;366(6462):250-254. doi: 10.1126/science.aax1522.
The unconventional -methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. 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.
非传统的 -甲基-D-天冬氨酸 (NMDA) 受体亚基 GluN3A 和 GluN3B，当与其他甘氨酸结合亚基 GluN1 结合时，可以产生仅由甘氨酸激活的兴奋性传导。然而，在天然成年组织中尚未鉴定出功能性 GluN1/GluN3 受体。我们发现 GluN1/GluN3A 受体在控制厌恶生理状态的内侧缰核 (MHb) 的成年小鼠神经元中起作用。在 MHb 中没有甘氨酸能神经元特化的情况下，胶质细胞通过 GluN1/GluN3A 受体调节神经元活性。减少 MHb 中的 GluN1/GluN3A 受体水平可防止位置厌恶条件作用。我们的研究通过证明其通过兴奋性甘氨酸能 NMDA 受体控制负价情感关联，扩展了甘氨酸的生理和行为意义。
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