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

in: Journal of Neuroscience (2022)
Tröger, Jessica; Seemann, Eric; Heintzmann, Rainer; Kessels, Michael; Qualmann, Britta
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 imaged receptor fields at ultra-high resolution at freeze-fractured membranes, tracked surface and internalized glycine receptors (GlyR) and studied differential regulations of GlyRβ interactions with the scaffold protein gephyrin and the F-BAR domain protein syndapin I and thereby reveal key principles of this process. S403 phosphorylation of GlyRβ, known to be triggered by synaptic signaling, caused a decoupling from gephyrin scaffolds but simultaneously promoted association of syndapin I with GlyRβ. In line, kainate-treatments used to trigger rearrangements of glycine receptors in murine syndapin I KO spinal cords (mixed sex) showed even more severe receptor field fragmentation than already observed in untreated syndapin I KO spinal cords. Syndapin I KO furthermore resulted in more dispersed receptors and increased receptor mobility also pointing out an important contribution of syndapin I in the organization of GlyRβ fields. Strikingly, syndapin I KO also led to a complete disruption of kainate-induced GlyRβ internalization. Accompanying quantitative ultra-high resolution studies in dissociated spinal cord neurons strongly suggested that the observed defects in GlyR internalization observed in syndapin I KO spinal cords are directly caused by syndapin I deficiency within murine spinal cord neurons. Together our results unveiled important mechanisms organizing and altering glycine receptor fields during both steady-state and particularly upon kainate-induced synaptic rearrangement - principles organizing and fine-tuning synaptic efficacy and plasticity of glycinergic synapses in the spinal cord.

Cookies & Skripte von Drittanbietern

Diese Website verwendet Cookies. Für eine optimale Performance, eine reibungslose Verwendung sozialer Medien und aus Werbezwecken empfiehlt es sich, der Verwendung von Cookies & Skripten durch Drittanbieter zuzustimmen. Dafür werden möglicherweise Informationen zu Ihrer Verwendung der Website von Drittanbietern für soziale Medien, Werbung und Analysen weitergegeben.
Weitere Informationen finden Sie unter Datenschutz und im Impressum.
Welchen Cookies & Skripten und der damit verbundenen Verarbeitung Ihrer persönlichen Daten stimmen Sie zu?

Sie können Ihre Einstellungen jederzeit unter Datenschutz ändern.