title: Glutamatergic synapses in the rat nucleus tractus solitarii develop by direct insertion of calcium-impermeable AMPA receptors and without activation of NMDA receptors.
abstract: Calcium influxes through ionotropic glutamate receptors (AMPA and NMDA receptors, AMPARs and NMDARs) are considered to be critical for the shaping and refinement of neural circuits during synaptogenesis. Using a combined morphological and electrophysiological approach, we evaluated this hypothesis at the level of the nucleus tractus solitarii (NTS), a brainstem structure that is a gateway for many visceral sensory afferent fibres. We confirmed that in the NTS, the first excitatory synapses appeared at embryonic day 18. We next characterized the biophysical properties of NTS AMPARs. Throughout perinatal development, both evoked and miniature EPSCs recorded in the presence of an NMDAR blocker were insensitive to polyamines and had linear current-voltage relationships. This demonstrated that AMPARs at NTS excitatory synapses were calcium-impermeable receptors composed of a majority of GluR2 subunits. We then investigated the influence of calcium influxes through NMDARs on the development of NTS synaptic transmission. We found that NMDAR expression at synaptic sites did not precede AMPAR expression. Moreover, NMDAR blockade in utero did not prevent the development of AMPAR synaptic currents and the synaptic clustering of GluR2 subunits. Thus, our data support an alternative model of synaptogenesis that does not depend on calcium influxes through either AMPARs or NMDARs. This model may be particularly relevant to the formation of neural networks devoted to basic behaviours required at birth for survival.
authors.affiliation: Laboratoire de Neurophysiologie Cellulaire, CNRS UMR 6150, IFR Jean-Roche, Faculté de Médecine, Bd Pierre Dramard, 13916 Marseille cedex 20, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Balland
authors.forename: Philippe
authors.initials: P
authors.lastname: Lachamp
authors.forename: Caroline
authors.initials: C
authors.lastname: Strube
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kessler
authors.forename: Fabien
authors.initials: F
authors.lastname: Tell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017552:Solitary Nucleus / Q000196:embryology* / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C118486:Grip2 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium