Spinal cord synaptic plasticity by GlyRβ release from receptor fields and syndapin-dependent uptake

Abstract

Glycine receptor-mediated inhibitory neurotransmission is key for spinal cord function. Recent observations suggested that by largely elusive mechanisms also glycinergic synapses display synaptic plasticity. We here identify syndapin I as critical player. Interestingly, syndapin I cooperates but in part also competes with gephyrin. Syndapin I deficiency led to fragmentation of glycine receptor fields, more disperse receptors and increased receptor mobility. Kainate treatment highlighted syndapin Is importance even more. Our analyses unveiled that PKC-mediated S403 phosphorylation-mediated glycine receptor {beta} decoupling from gephyrin scaffolds simultaneously promoted syndapin I association. In line, kainate-treated syndapin I KO spinal cords showed even more severe receptor field fragmentation. Furthermore, syndapin I deficiency completely disrupted kainate-induced glycine receptor internalization. Together, this unveiled important mechanisms controlling the number and organization of glycine receptor fields at inhibitory postsynapses during both steady-state and kainate-induced synaptic rearrangement - principles organizing and fine-tuning synaptic efficacy of inhibitory synapses in the spinal cord.