GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits.
GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits.
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GluN3A兴奋性甘氨酸受体控制成人皮质和杏仁核回路。
DOI：
10.1016/j.neuron.2022.05.016
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发表时间：
2022-08-03
期刊：
影响因子：
16.2
通讯作者：
Rebola, Nelson
中科院分区：
文献类型：
--
作者：
Bossi, Simon;Dhanasobhon, Dhanasak;Ellis-Davies, Graham C. R.;Frontera, Jimena;Van Velze, Marcel de Brito;Lourenco, Joana;Murillo, Alvaro;Lujan, Rafael;Casado, Mariano;Perez-Otano, Isabel;Bacci, Alberto;Popa, Daniela;Paoletti, Pierre;Rebola, Nelson
关键词：
GluN 3A是NMDA受体（NMDAR）的非典型甘氨酸结合亚基，其在脑中的作用大多未知。在这里，我们表明，GluN 3A亚基的表达控制兴奋性小鼠成年皮层和杏仁核电路通过一个不寻常的信号机制，涉及兴奋性甘氨酸GluN 1/GluN 3A受体（eGlyRs）的形成和他们的紧张激活细胞外甘氨酸。eGlyR主要位于突触外，并存在于特定的神经元群体中，包括基底外侧杏仁核（BLA）的主细胞和新皮质的SST阳性中间神经元（SST-IN）。在BLA中，紧张性eGlyR电流对恐惧调节协议敏感，受到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-IN的体内尖峰和皮层活动的行为依赖性调制。因此，含有GluN 3A的eGlyRs代表了成人大脑中一种新的和广泛的信号传导方式，其属性与常规NMDAR的属性明显不同。在小鼠中，GluN 3A由皮质中的SST-INs表达，BLA中的锥体神经元GluN 3A组装为兴奋性甘氨酸GluN 1/GluN 3A受体（eGlyRs）eGlyRs检测细胞外甘氨酸水平并产生紧张性兴奋电流eGlyRs调节皮质中SST-INs的功能并改变BLA Bossi等人恐惧记忆的形成。显示GluN 3A亚基通过兴奋性甘氨酸GluN 1/GluN 3A受体（eGlyRs）的形成控制成年小鼠脑中选择性神经元群体的活性。功能分析表明，eGlyRs调节新皮层生长抑素阳性中间神经元的募集，并参与BLA中恐惧记忆的稳定性。
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. In mice, GluN3A is expressed by SST-INs in the cortex and pyramidal neurons in the BLA GluN3A assembles as excitatory glycine GluN1/GluN3A receptors (eGlyRs) eGlyRs detect extracellular glycine levels and generate tonic excitatory currents eGlyRs tune the function of SST-INs in cortex and alter the formation of fear memories in BLA Bossi et al. show that GluN3A subunits control the activity of selective neuronal populations in the adult mouse brain via the formation of excitatory glycine GluN1/GluN3A receptors (eGlyRs). Functional analysis reveals that eGlyRs regulate the recruitment of somatostatin-positive interneurons in the neocortex and participate in the stability of fear memories in the BLA.
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