Ca2+-permeable AMPA receptors and spontaneous presynaptic transmitter release at developing excitatory spinal synapses

At many mature vertebrate glutamatergic synapses, excitatory transmission s trength 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 postsyn aptic Ca2+ influx during early development. However, the development of syn aptic receptor expression and colocalization has been examined developmenta lly in only a few systems, and changes in release properties at neuronal sy napses have not been characterized extensively. We recorded miniature EPSCs (mEPSCs) from spinal interneurons in Xenopus embryos and larvae. In mature 5-8 d larvae, similar to 70% of mEPSCs in Mg2+-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 similar to 65% of mEPSCs are exclusively fast, suggesting that t hese synapses initially express predominantly AMPA-R. In a physiological Mg 2+ concentration (1 mM), mEPSCs throughout development are mainly AMPA-R-me diated at negative potentials. Embryonic synaptic AMPA-R are highly Ca2+-pe rmeable, mEPSC amplitude is over twofold larger than at mature synapses, an d mEPSCs frequently occur in bursts consistent with asynchronous multiquant al release. AMPA-R function in this motor pathway thus appears to be indepe ndent of previous NMDA-R activation, unlike other regions of the developing nervous system, ensuring a greater reliability for embryonic excitatory tr ansmission. Early spontaneous excitatory activity is specialized to promote AMPA-R-mediated synaptic Ca2+ influx, which likely has significant roles i n neuronal development.