Differential postnatal maturation of GABAA, glycine receptor, and mixed synaptic currents in Renshaw cells and ventral spinal interneurons.
Renshaw cells (RCs) receive excitatory inputs from motoneurons to which then they inhibit. The gain of this spinal recurrent inhibitory circuit is modulated by inhibitory synapses on RCs. Inhibitory synapses on RCs mature postnatally, developing unusually large postsynaptic gephyrin clusters that colocalize glycine and GABA(A) receptors. We hypothesized that these features potentiate inhibitory currents in RCs. Thus, we analyzed glycinergic and GABAergic "inhibitory" miniature postsynaptic currents (mPSCs) in neonatal [postnatal day 1 (P1) to P5] and mature (P9-P15) RCs and compared them to other ventral interneurons (non-RCs). Recorded neurons were Neurobiotin filled and identified as RCs or non-RCs using post hoc immunohistochemical criteria. Glycinergic, GABAergic, and mixed glycine/GABA mPSCs matured differently in RCs and non-RCs. In RCs, glycinergic and GABA(A) mPSC peak amplitudes increased 230 and 45%, respectively, from P1-P5 to P9-P15, whereas in non-RCs, glycinergic peak amplitudes changed little and GABA(A) amplitudes decreased. GABA(A) mPSCs were slower in RCs (P1-P5, tau = 58 ms; P9-P15, tau = 43 ms) compared with non-RCs (P1-P5, tau = 27 ms; P9-P15, tau = 14 ms). Thus, fast glycinergic currents dominated "mixed" mPSC peak amplitudes in mature RCs, and GABA(A) currents dominated their long decays. In non-RCs, GABAergic and mixed events had shorter durations, and their frequencies decreased with development. Functional maturation of inhibitory synapses on RCs correlates well with increased glycine receptor recruitment to large gephyrin patches, colocalization with alpha3/alpha5-containing GABA(A) receptors, and maintenance of GABA/glycine corelease. As a result, charge transfer in GABA, glycine, or mixed mPSCs was larger in mature RCs than in non-RCs, suggesting RCs receive potent inhibitory synapses.
González-Forero
David
D
Department of Anatomy and Physiology, Wright State University, Dayton, Ohio 45435, USA.
Alvarez
Francisco J
FJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000870:Anterior Horn Cells / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D015415:Biomarkers; D064026:Calbindins; D007091:Image Processing, Computer-Assisted; D007395:Interneurons / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000032:analysis; D018613:Microscopy, Confocal; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D018009:Receptors, Glycine / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D013116:Spinal Cord / Q000166:cytology* / Q000254:growth & development; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D050494:Vesicular Acetylcholine Transport Proteins
D015415:Biomarkers; D064026:Calbindins; D026901:Membrane Transport Proteins; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D064030:S100 Calcium Binding Protein G; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D013331:Strychnine; D014403:Tubocurarine; D001640:Bicuculline
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