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

Science Advances (2022)

Angela M Getz, Mathieu Ducros, Christelle Breillat, Aurélie Lampin-Saint-Amaux, Sophie Daburon, Urielle François, Agata Nowacka, Mónica Fernández-Monreal, Eric Hosy, Frédéric Lanore, Hanna L Zieger, Matthieu Sainlos, Yann Humeau, Daniel Choquet

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 (AMPARs) as a model, we generated a knock-in mouse expressing the biotin acceptor peptide (AP) tag on the GluA2 extracellular N-terminal. 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 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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