Washbourne Philip, Bennett Jennie E, McAllister A Kimberley
Center for Neuroscience, University of California Davis, 1544 Newton Ct., Davis, California 95616, USA.
Nat Neurosci. 2002 Aug;5(8):751-9. doi: 10.1038/nn883.
Although many of the molecules involved in synaptogenesis have been identified, the sequence and kinetics of synapse assembly in the central nervous system (CNS) remain largely unknown. We used simultaneous time-lapse imaging of fluorescent glutamate receptor subunits and presynaptic proteins in rat cortical neurons in vitro to determine the dynamics and time course of N-methyl-D-aspartate receptor (NMDAR) recruitment to nascent synapses. We found that both NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits are present in mobile transport packets in neurons before and during synaptogenesis. NMDAR transport packets are more mobile than AMPAR subunits, moving along microtubules at about 4 microm/min, and are recruited to sites of axodendritic contact within minutes. Whereas NMDAR recruitment to new synapses can be either concurrent with or independent of the protein PSD-95, AMPARs are recruited with a slower time course. Thus, glutamatergic synapses can form rapidly by the sequential delivery of modular transport packets containing glutamate receptors.
尽管参与突触形成的许多分子已被识别，但中枢神经系统（CNS）中突触组装的顺序和动力学仍 largely 未知。我们利用体外大鼠皮层神经元中荧光谷氨酸受体亚基和突触前蛋白的同步延时成像，来确定 N-甲基-D-天冬氨酸受体（NMDAR）募集到新生突触的动力学和时间进程。我们发现，在突触形成之前和期间，NMDA 和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）亚基都存在于神经元中的移动运输小泡中。NMDAR 运输小泡比 AMPAR 亚基更具移动性，以约 4 微米/分钟的速度沿着微管移动，并在数分钟内被募集到轴突树突接触部位。虽然 NMDAR 募集到新突触可以与蛋白 PSD-95 同时发生或独立于它，但 AMPAR 的募集时间进程较慢。因此，谷氨酸能突触可以通过顺序递送含有谷氨酸受体的模块化运输小泡而迅速形成。
