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Development/Plasticity/Repair Regulation of Gephyrin Cluster Size and Inhibitory Synaptic

Summary: Development/Plasticity/Repair
Regulation of Gephyrin Cluster Size and Inhibitory Synaptic
Currents on Renshaw Cells by Motor Axon Excitatory Inputs
David Gonzalez-Forero,1,2 Angel M. Pastor,2 Eric J. Geiman,1 Beatriz BeniŽtez-Temin~o,2 and Francisco J. Alvarez1
1Department of Anatomy and Physiology, Wright State University, Dayton, Ohio 45435, and 2Departamento de FisiologiŽa y ZoologiŽa, Facultad de BiologiŽa,
Universidad de Sevilla, 41012-Sevilla, Spain
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 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 P9­P15 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 ampli-
tude 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 GABAA 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, GABAA receptors.


Source: Alvarez, Francisco J. - Department of Neuroscience, Cell Biology, and Physiology, Wright State University


Collections: Biology and Medicine