Identification of a stereotypic molecular arrangement of glycine receptors at native spinal cord synapses

• Published in: bioRxiv
• Main Authors: Maynard, Stephanie A, Rostaing, Philippe, Gemin, Olivier, Candat, Adrien, Dumoulin, Andréa, Schaefer, Natascha, Villmann, Carmen, Triller, Antoine, Specht, Christian G
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 10.09.2021
• Subjects: Brain stem; Dorsal horn; Electron microscopy; Glycine receptors; Neurotransmission; Neurotransmitter receptors; Spinal cord; Startle response
• DOI: 10.1101/2021.09.09.459599

Precise quantitative information about the molecular architecture of synapses is essential to understanding the functional specificity and downstream signaling processes at specific populations of synapses. Glycine receptors (GlyRs) are the primary fast inhibitory neurotransmitter receptors in the spinal cord and brain stem. These inhibitory glycinergic networks crucially regulate motor and sensory processes. Thus far the nanoscale organization of GlyRs underlying the different network specificities has not been defined. Here, we have quantitatively characterized the molecular arrangement and ultra-structure of glycinergic synapses in native spinal cord tissue using quantitative super-resolution correlative light and electron microscopy (SR-CLEM). We show that GlyRs exhibit equal receptor-scaffold occupancy and constant absolute packing densities of about 2000 GlyRs μm-2 at synapses across the spinal cord and throughout adulthood, even though ventral horn synapses have twice the total copy numbers, larger postsynaptic domains and more convoluted morphologies than dorsal horn synapses. We demonstrate that this stereotypic molecular arrangement is maintained at glycinergic synapses in the oscillator mouse model of the neuromotor disease hyperekplexia despite a decrease in synapse size, indicating that the molecular organization of GlyRs is preserved in this hypomorph. We thus conclude that the morphology and size of inhibitory PSDs rather than differences in GlyR packing determine the postsynaptic strength of glycinergic neurotransmission in motor and sensory spinal cord networks.