Department of Pharmacology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Neural Dev. 2012 Feb 16;7:8. doi: 10.1186/1749-8104-7-8.
Neocortical circuits are established through the formation of synapses between cortical neurons, but the molecular mechanisms of synapse formation are only beginning to be understood. The mechanisms that control synaptic vesicle (SV) and active zone (AZ) protein assembly at developing presynaptic terminals have not yet been defined. Similarly, the role of glutamate receptor activation in control of presynaptic development remains unclear.
Here, we use confocal imaging to demonstrate that NMDA receptor (NMDAR) activation regulates accumulation of multiple SV and AZ proteins at nascent presynaptic terminals of visual cortical neurons. NMDAR-dependent regulation of presynaptic assembly occurs even at synapses that lack postsynaptic NMDARs. We also provide evidence that this control of presynaptic terminal development is independent of glia.
Based on these data, we propose a novel NMDAR-dependent mechanism for control of presynaptic terminal development in excitatory neocortical neurons. Control of presynaptic development by NMDARs could ultimately contribute to activity-dependent development of cortical receptive fields.
新皮质电路是通过皮质神经元之间形成突触而建立的，但突触形成的分子机制才刚刚开始被理解。控制发育中突触前末端突触小泡 (SV) 和活性区 (AZ) 蛋白组装的机制尚未确定。同样，谷氨酸受体激活在控制突触前发育中的作用仍不清楚。
在这里，我们使用共聚焦成像来证明 NMDA 受体 (NMDAR) 激活调节视觉皮层神经元新生突触前末端的多个 SV 和 AZ 蛋白的积累。即使在缺乏突触后 NMDAR 的突触上，NMDAR 依赖性的突触前组装调节也会发生。我们还提供了证据表明，这种对突触前末端发育的控制与神经胶质无关。
基于这些数据，我们提出了一种新的 NMDA 依赖性机制，用于控制兴奋性新皮质神经元的突触前末端发育。NMDAR 对突触前发育的控制最终可能有助于皮质感受野的活动依赖性发育。
