title: Ca(2+)-permeable AMPA receptors and spontaneous presynaptic transmitter release at developing excitatory spinal synapses.
abstract: 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.
authors.affiliation: Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rohrbough
authors.forename: N C
authors.initials: NC
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D007814:Larva; D008274:Magnesium / Q000494:pharmacology / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology*; D011930:Reaction Time; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium; D007608:Kainic Acid; D002118:Calcium