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

Kalina T Haas | Benjamin Compans | Mathieu Letellier | Thomas M Bartol | Dolors Grillo-Bosch | Terrence J Sejnowski | Matthieu Sainlos | Daniel Choquet | Olivier Thoumine | Eric Hosy
eLife | 2018

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.

Pubmed ID: 30044218

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: European Research Council, International
    Id: 232942
  • Agency: European Research Council, International
    Id: 339541
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103712
  • Agency: Agence Nationale de la Recherche, International
    Id: NanoDom
  • Agency: H2020 European Research Council, International
    Id: nano-dyn-syn

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