High-resolution imaging and manipulation of endogenous AMPA receptor surface mobility during synaptic plasticity and learning

Getz, A. M.; Ducros, M.; Breillat, C.; Lampin-Saint-Amaux, A.; Daburon, S.; Francois, U.; Nowacka, A.; Fernandez-Monreal, M.; Hosy, E.; Lanore, F.; Zieger, H.; Sainlos, M.; Humeau, Y.; Choquet, D.

doi:10.1101/2021.09.21.461215

bioRxiv · 10.1101/2021.09.21.461215

High-resolution imaging and manipulation of endogenous AMPA receptor surface mobility during synaptic plasticity and learning

Getz, A. M.·Ducros, M.·Breillat, C.·Lampin-Saint-Amaux, A.·Daburon, S.·Francois, U.·Nowacka, A.·Fernandez-Monreal, M.·Hosy, E.·Lanore, F.·Zieger, H.·Sainlos, M.·Humeau, Y.·Choquet, D.

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Abstract

Regulation of synaptic neurotransmitter receptor content is a fundamental mechanism for tuning synaptic efficacy during experience-dependent plasticity and behavioral adaptation. However, experimental approaches to track and modify receptor movements in integrated experimental systems are limited. Exploiting AMPA-type glutamate receptors (AMPAR) as a model, we generated a knock-in mouse expressing the biotin acceptor peptide (AP) tag on the GluA2 extracellular N-terminus. Cell-specific introduction of biotin ligase allows the use of monovalent or tetravalent avidin variants to respectively monitor or manipulate the surface mobility of endogenous AMPAR containing biotinylated AP-GluA2 in neuronal subsets. AMPAR immobilization precluded the expression of long-term potentiation and formation of contextual fear memory, allowing for target-specific control of the expression of synaptic plasticity and animal behavior. The AP tag knock-in model offers unprecedented access to resolve and control the spatiotemporal dynamics of endogenous receptors, and opens new avenues to study the molecular mechanisms of synaptic plasticity and learning.

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Getz, A. M., Ducros, M., Breillat, C., Lampin-Saint-Amaux, A., Daburon, S., Francois, U., Nowacka, A., Fernandez-Monreal, M., Hosy, E., Lanore, F., Zieger, H., Sainlos, M., Humeau, Y., Choquet, D.. 2021-09-22. High-resolution imaging and manipulation of endogenous AMPA receptor surface mobility during synaptic plasticity and learning. https://doi.org/10.1101/2021.09.21.461215

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