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

eLife

Stephanie A Maynard¹  Andréa Dumoulin¹  Adrien Candat¹  Antoine Triller¹  Philippe Rostaing¹  Olivier Gemin¹  Christian G Specht²  Natascha Schaefer³  Carmen Villmann³ 

[1] Institut de Biologie de l'ENS (IBENS), École Normale Supérieure, CNRS, Inserm, PSL University, Paris, France;Institut de Biologie de l'ENS (IBENS), École Normale Supérieure, CNRS, Inserm, PSL University, Paris, France;Diseases and Hormones of the Nervous System (DHNS), Inserm U1195, Université Paris-Saclay, Paris, France;Institute for Clinical Neurobiology, University Hospital, Julius-Maximilians-University, Wuerzburg, Germany;

关键词: single molecule localization microscopy;    correlative light and electron microscopy;    electron microscopy;    hyperekplexia;    oscillator mouse model;    glycine receptor;    spinal cord;    Mouse;   

DOI  :  10.7554/eLife.74441

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 brainstem. 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 spinal cord tissue using quantitative super-resolution correlative light and electron microscopy. We show that endogenous GlyRs exhibit equal receptor-scaffold occupancy and constant 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 postsynaptic specializations rather than differences in GlyR packing determine the postsynaptic strength of glycinergic neurotransmission in motor and sensory spinal cord networks.

【 授权许可】

CC BY