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Controlling synapse differentiation with light - eLife, April 2020

Controlling synapse differentiation with light - eLife, April 2020


Optogenetic control of excitatory post-synaptic differentiation through neuroligin-1 tyrosine phosphorylation

Neuroligins (Nlgns) are adhesion proteins mediating trans-synaptic contacts in neurons. However, conflicting results around their role in synaptic differentiation arise from the various techniques used to manipulate Nlgn expression level. Orthogonally to these approaches, we triggered here the phosphorylation of endogenous Nlgn1 in CA1 mouse hippocampal neurons using a photoactivatable tyrosine kinase receptor (optoFGFR1). Light stimulation for 24 hr selectively increased dendritic spine density and AMPA-receptor-mediated EPSCs in wild-type neurons, but not in Nlgn1 knock-out neurons or when endogenous Nlgn1 was replaced by a non-phosphorylatable mutant (Y782F). Moreover, light stimulation of optoFGFR1 partially occluded LTP in a Nlgn1-dependent manner. Combined with computer simulations, our data support a model by which Nlgn1 tyrosine phosphorylation promotes the assembly of an excitatory post-synaptic scaffold that captures surface AMPA receptors. This optogenetic strategy highlights the impact of Nlgn1 intracellular signaling in synaptic differentiation and potentiation, while enabling an acute control of these mechanisms.

CA1 neurons in a mouse organotypic slice that were single-cell electroporated with tdTomato as a volume marker and observed by confocal microscopy at the Bordeaux Imaging Center.


Authors: Letellier M, Lagardère M, Tessier B, Janovjak H, Thoumine O.

- Publication on Elife. 2020 Apr 23;9. pii: e52027. doi: 10.7554/eLife.52027.
- Contacts: Mathieu Letellier and Olivier Thoumine

+ Cf Bordeaux Neurocampus website here