Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, Université PSL, CNRS, INSERM, F-75005 Paris, France.
Sorbonne Université, Institut Du Cerveau-Paris Brain Institute-ICM, Inserm U1127, CNRS UMR 7225, 47 Boulevard de l'Hôpital, 75013 Paris, France.
Neuron. 2022 Aug 3;110(15):2438-2454.e8. doi: 10.1016/j.neuron.2022.05.016. Epub 2022 Jun 13.
GluN3A is an atypical glycine-binding subunit of NMDA receptors (NMDARs) whose actions in the brain are mostly unknown. Here, we show that the expression of GluN3A subunits controls the excitability of mouse adult cortical and amygdalar circuits via an unusual signaling mechanism involving the formation of excitatory glycine GluN1/GluN3A receptors (eGlyRs) and their tonic activation by extracellular glycine. eGlyRs are mostly extrasynaptic and reside in specific neuronal populations, including the principal cells of the basolateral amygdala (BLA) and SST-positive interneurons (SST-INs) of the neocortex. In the BLA, tonic eGlyR currents are sensitive to fear-conditioning protocols, are subject to neuromodulation by the dopaminergic system, and control the stability of fear memories. In the neocortex, eGlyRs control the in vivo spiking of SST-INs and the behavior-dependent modulation of cortical activity. GluN3A-containing eGlyRs thus represent a novel and widespread signaling modality in the adult brain, with attributes that strikingly depart from those of conventional NMDARs.
GluN3A 是 NMDA 受体（NMDARs）的一种非典型甘氨酸结合亚基，其在大脑中的作用大多未知。在这里，我们表明 GluN3A 亚基的表达通过一种涉及形成兴奋性甘氨酸 GluN1/GluN3A 受体（eGlyRs）及其由细胞外甘氨酸引起的紧张性激活的不寻常信号机制来控制成年小鼠大脑皮质和杏仁核回路的兴奋性。eGlyRs 主要位于突触外，存在于特定的神经元群体中，包括杏仁核基底外侧核（BLA）的主要细胞和新皮层中的 SST 阳性中间神经元（SST-INs）。在 BLA 中，紧张性 eGlyR 电流对恐惧条件反射方案敏感，受多巴胺能系统的神经调节，并控制恐惧记忆的稳定性。在新皮层中，eGlyRs 控制 SST-INs 的体内放电和皮层活动的行为依赖性调节。因此，含有 GluN3A 的 eGlyRs 代表了成年大脑中的一种新型广泛的信号传递方式，其属性与传统的 NMDARs 明显不同。
