Pre-post synaptic alignment through neuroligin tunes synaptic transmission efficiency

Hosy, E.; Choquet, D.; Bartol, T. M.; Sejnowski, T. J.; Thoumine, O.; Letellier, M.; Compans, B.; Haas, K.; Grillo-Bosch, D.; Sainlos, M.

doi:10.1101/189407

bioRxiv · 10.1101/189407

Pre-post synaptic alignment through neuroligin tunes synaptic transmission efficiency

Hosy, E.·Choquet, D.·Bartol, T. M.·Sejnowski, T. J.·Thoumine, O.·Letellier, M.·Compans, B.·Haas, K.·Grillo-Bosch, D.·Sainlos, M.

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Abstract

The nanoscale organization of neurotransmitter receptors relative to pre-synaptic release sites is a fundamental determinant of both the amplitude and reliability of synaptic transmission. How modifications in the alignment between pre- and post-synaptic machineries affect synaptic current properties has only been addressed with computer modeling, and therefore remains hypothetical. Using dual-color single molecule based 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 C-terminal truncated form of NLG1 disrupted this correlation without affecting the intrinsic organization of AMPAR nanodomains. Moreover, this NLG1 dominant-negative mutant significantly shifted the pre-synaptic release machinery from AMPAR synaptic clusters. Electrophysiology and computer modeling show that this physical shift is sufficient to induce a significant decrease in synaptic transmission. Thus, our results suggest the necessity for synapses to release glutamate in front of AMPAR nanodomains, to maintain a high efficiency of synaptic responses.

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Hosy, E., Choquet, D., Bartol, T. M., Sejnowski, T. J., Thoumine, O., Letellier, M., Compans, B., Haas, K., Grillo-Bosch, D., Sainlos, M.. 2017-09-15. Pre-post synaptic alignment through neuroligin tunes synaptic transmission efficiency. https://doi.org/10.1101/189407

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