Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency

eLife

Thomas M Bartol¹  Benjamin Compans¹  Olivier Thoumine¹  Terrence J Sejnowski¹  Matthieu Sainlos²  Eric Hosy²  Daniel Choquet³  Kalina T Haas³  Dolors Grillo-Bosch³  Mathieu Letellier³ 

[1] Interdisciplinary Institute for Neuroscience, CNRS, UMR 5297, F-33000, Bordeaux, France;Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States;Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000, Bordeaux, France;

关键词: AMPA receptors;    super-resolution microscopy;    synaptic transmission;   

DOI  :  10.7554/eLife.31755

来源: DOAJ

【 摘 要 】

The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses efficiency.

【 授权许可】

Unknown