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

• DOI: 10.7554/elife.31755
• Publication Date: 2018-07-25T12:00:20Z
• Authors: Kalina T Haas; Benjamin Compans; Mathieu Letellier; Thomas M Bartol; Dolors Grillo-Bosch; Terrence J Sejnowski; Matthieu Sainlos; Daniel Choquet; Olivier Thoumine; Eric Hosy
• Keywords: Neuroligin; Synaptic scaling; Synaptic cleft; Silent synapse

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