Rohrbough J, Spitzer N C
Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093, USA.
J Neurosci. 1999 Oct 1;19(19):8528-41. doi: 10.1523/JNEUROSCI.19-19-08528.1999.
At many mature vertebrate glutamatergic synapses, excitatory transmission strength and plasticity are regulated by AMPA and NMDA receptor (AMPA-R and NMDA-R) activation and by patterns of presynaptic transmitter release. Both receptors potentially direct neuronal differentiation by mediating postsynaptic Ca(2+) influx during early development. However, the development of synaptic receptor expression and colocalization has been examined developmentally in only a few systems, and changes in release properties at neuronal synapses have not been characterized extensively. We recorded miniature EPSCs (mEPSCs) from spinal interneurons in Xenopus embryos and larvae. In mature 5-8 d larvae, approximately 70% of mEPSCs in Mg(2+)-free saline are composed of both a fast AMPA-R-mediated component and a slower NMDA-R-mediated decay, indicating receptor colocalization at most synapses. By contrast, in 39-40 hr embryos approximately 65% of mEPSCs are exclusively fast, suggesting that these synapses initially express predominantly AMPA-R. In a physiological Mg(2+) concentration (1 mM), mEPSCs throughout development are mainly AMPA-R-mediated at negative potentials. Embryonic synaptic AMPA-R are highly Ca(2+)-permeable, mEPSC amplitude is over twofold larger than at mature synapses, and mEPSCs frequently occur in bursts consistent with asynchronous multiquantal release. AMPA-R function in this motor pathway thus appears to be independent of previous NMDA-R activation, unlike other regions of the developing nervous system, ensuring a greater reliability for embryonic excitatory transmission. Early spontaneous excitatory activity is specialized to promote AMPA-R-mediated synaptic Ca(2+) influx, which likely has significant roles in neuronal development.
在许多成熟的脊椎动物谷氨酸能突触中，兴奋性传递强度和可塑性受AMPA和NMDA受体（AMPA-R和NMDA-R）激活以及突触前递质释放模式的调节。在早期发育过程中，这两种受体都可能通过介导突触后Ca(2+)内流来指导神经元分化。然而，仅在少数系统中对突触受体表达和共定位的发育情况进行了研究，并且尚未广泛表征神经元突触释放特性的变化。我们记录了非洲爪蟾胚胎和幼体脊髓中间神经元的微小兴奋性突触后电流（mEPSCs）。在成熟的5-8日龄幼体中，无镁盐溶液中约70%的mEPSCs由快速的AMPA-R介导成分和较慢的NMDA-R介导衰减组成，这表明大多数突触处受体共定位。相比之下，在39-40小时龄的胚胎中，约65%的mEPSCs仅为快速成分，这表明这些突触最初主要表达AMPA-R。在生理镁离子浓度（1 mM）下，整个发育过程中的mEPSCs在负电位时主要由AMPA-R介导。胚胎突触AMPA-R具有高度的Ca(2+)通透性，mEPSC幅度比成熟突触时大两倍以上，并且mEPSCs经常以爆发形式出现，这与异步多量子释放一致。因此，与发育中的神经系统的其他区域不同，该运动通路中的AMPA-R功能似乎独立于先前的NMDA-R激活，从而确保胚胎兴奋性传递具有更高的可靠性。早期自发兴奋性活动专门促进AMPA-R介导的突触Ca(2+)内流，这可能在神经元发育中发挥重要作用。
