Regulation of gephyrin cluster size and inhibitory synaptic currents on Renshaw cells by motor axon excitatory inputs.
Renshaw cells receive a high density of inhibitory synapses characterized by large postsynaptic gephyrin clusters and mixed glycinergic/GABAergic inhibitory currents with large peak amplitudes and long decays. These properties appear adapted to increase inhibitory efficacy over Renshaw cells and mature postnatally by mechanisms that are unknown. We tested the hypothesis that heterosynaptic influences from excitatory motor axon inputs modulate the development of inhibitory synapses on Renshaw cells. Thus, tetanus (TeNT) and botulinum neurotoxin A (BoNT-A) were injected intramuscularly at postnatal day 5 (P5) to, respectively, elevate or reduce motor axon firing activity for approximately 2 weeks. After TeNT injections, the average gephyrin cluster areas on Renshaw cells increased by 18.4% at P15 and 28.4% at P20 and decreased after BoNT-A injections by 17.7% at P15 and 19.9% at P20. The average size differences resulted from changes in the proportions of small and large gephyrin clusters. Whole-cell recordings in P9-P15 Renshaw cells after P5 TeNT injections showed increases in the peak amplitude of glycinergic miniature postsynaptic currents (mPSCs) and the fast component of mixed (glycinergic/GABAergic) mPSCs compared with controls (60.9% and 78.9%, respectively). GABAergic mPSCs increased in peak amplitude to a smaller extent (45.8%). However, because of the comparatively longer decays of synaptic GABAergic currents, total current transfer changes after TeNT were similar for synaptic glycine and GABA(A) receptors (56 vs 48.9% increases, respectively). We concluded that motor axon excitatory synaptic activity modulates the development of inhibitory synapse properties on Renshaw cells, influencing recruitment of postsynaptic gephyrin and glycine receptors and, to lesser extent, GABA(A) receptors.
Gonzalez-Forero
David
D
Department of Anatomy and Physiology, Wright State University, Dayton, Ohio 45435, USA.
Pastor
Angel M
AM
Geiman
Eric J
EJ
Benítez-Temiño
Beatriz
B
Alvarez
Francisco J
FJ
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry* / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D005998:Glycine / Q000502:physiology; D007395:Interneurons / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry* / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D046912:Multiprotein Complexes / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013744:Tetanus Toxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002352:Carrier Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D013744:Tetanus Toxin; C073441:gephyrin; C033652:postsynaptic density proteins; D005680:gamma-Aminobutyric Acid; D019274:Botulinum Toxins, Type A; D005998:Glycine