Differential Postnatal Maturation of GABAA, Glycine Receptor, and Mixed Synaptic Currents in Renshaw Cells and Ventral Spinal Interneurons

David González-Forero, Francisco J. Alvarez

Research output: Contribution to journalArticlepeer-review

Abstract

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, τ = 58 ms; P9-P15, τ = 43 ms) compared with non-RCs (P1-P5, τ = 27 ms; P9-P15, τ = 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 α3/α5-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.

Original languageEnglish
Pages (from-to)2010-2023
Number of pages14
JournalJournal of Neuroscience
Volume25
Issue number8
DOIs
StatePublished - Feb 23 2005

ASJC Scopus Subject Areas

  • General Neuroscience

Keywords

  • 6-Cyano-7nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Anterior Horn Cells / physiology
  • Bicculline / pharmacology
  • Biomarkers
  • Calbindins
  • Image Processing, Computer-Assisted
  • Interneurons / physiology*
  • Membrane Transport Proteins / analysis
  • Microscopy, Confocal
  • Rats
  • Recepetors, GABA-S / physiology*
  • Receptors, Glycine /
  • S100 Calcium Binding Protein G / analysis
  • Spinal Cord / cytology*
  • Spinal Cord / growth & development
  • Strychnine / pharmacology
  • Synaptic Transmission / physiology*
  • Tetrodotoxin / pharmacology
  • Tubocurarine / pharmacology
  • Vesicular Acetylcholine Transport Proteins
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Membrane Transport Proteins
  • Receptors, GABA-A
  • Receptors, Glycine
  • S100 Calcium Binding Protein G
  • SlC18a3 protein, rat
  • Tetrodotoxin
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Strychnine
  • Tubocurarine
  • Bicuculline

Disciplines

  • Medical Cell Biology
  • Medical Neurobiology
  • Medical Physiology
  • Neurosciences
  • Physiological Processes

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