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 ultrahigh-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 KO spinal cords (mixed sex) showed even more severe receptor field fragmentation than already observed in untreated KO spinal cords. Syndapin I deficiency furthermore resulted in more dispersed receptors and increased receptor mobility, also pointing out an important contribution of syndapin I to the organization of GlyRβ fields. Strikingly, KO also led to a complete disruption of kainate-induced GlyRβ internalization. Accompanying quantitative ultrahigh-resolution studies in dissociated spinal cord neurons proved that the defects in GlyR internalization observed in KO spinal cords are neuron-intrinsic defects caused by syndapin I deficiency. Together, our results unveiled important mechanisms organizing and altering glycine receptor fields during both steady state and particularly also as a consequence of kainate-induced synaptic rearrangement - principles organizing and fine-tuning synaptic efficacy and plasticity of glycinergic synapses in the spinal cord. Initial observations suggested that also glycinergic synapses, key for spinal cord and brainstem functions, may display some form of synaptic plasticity. Imaging receptor fields at ultrahigh-resolution at freeze-fractured membranes, tracking surface and internalized glycine receptors (GlyR) and studying regulations of GlyRβ interactions, we here reveal key principles of these kainate-inducible adaptations. A switch from gephyrin-mediated receptor scaffolding to syndapin I-mediated GlyRβ scaffolding and internalization allows for modulating synaptic receptor availability. In line, kainate-induced GlyRβ internalization was completely disrupted and GlyRβ receptor fields were distorted by KO. These results unveiled important mechanisms during both steady-state and kainate-induced alterations of synaptic GlyR fields, principles underlying synaptic efficacy and plasticity of synapses in the spinal cord.
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http://dx.doi.org/10.1523/JNEUROSCI.2060-21.2022 | DOI Listing |
Eur Radiol Exp
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Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
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Department of Neurosurgery, University of Arizona College of Medicine, 1111 Mc Dowell Road, Phoenix, AZ, 85006, USA.
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Investig Clin Urol
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Department of Spinal Neurosurgery, Gangnam Severance Hospital, Seoul, Korea.
Purpose: This study aims to develop and implement an economic evaluation using a micro-costing approach to provide a precise and transparent analysis of the direct costs of cystoscopic procedures in Korean hospitals. The study seeks to identify key cost components and evaluate whether current reimbursement rates accurately reflect these direct costs.
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Cureus
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Treatment Resistant Schizophrenia Outpatient Clinic, Júlio de Matos Hospital, São José Local Health Unit, Clinical Academic Center of Lisbon, Lisbon, PRT.
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View Article and Find Full Text PDFFood Nutr Res
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