title: Optical inactivation of synaptic AMPA receptors erases fear memory.
abstract: The synaptic delivery of neurotransmitter receptors, such as GluA1 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, mediates important processes in cognitive function, including memory acquisition and retention. Understanding the roles of these receptors has been hampered by the lack of a method to inactivate them in vivo with high spatiotemporal precision. We developed a technique to inactivate synaptic GluA1 AMPA receptors in vivo using chromophore-assisted light inactivation (CALI). We raised a monoclonal antibody specific for the extracellular domain of GluA1 that induced effective CALI when conjugated with a photosensitizer (eosin). Mice that had been injected in the CA1 hippocampal region with the antibody conjugate underwent a fear memory task. Exposing the hippocampus to green light using an implanted cannula erased acquired fear memory in the animals by inactivation of synaptic GluA1. Our optical technique for inactivating synaptic proteins will enable elucidation of their physiological roles in cognition.
authors.affiliation: Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, Japan.|Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Takemoto
authors.affiliation: The University of Tokyo, Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), Meguro-ku, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.affiliation: Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tada
authors.affiliation: Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Suyama
authors.affiliation: Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Sano
authors.affiliation: Osaka University, The Institute of Scientific and Industrial Research, Ibaraki, Osaka, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Nagai
authors.affiliation: The University of Tokyo, Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), Meguro-ku, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.affiliation: Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D005108:Extinction, Psychological / Q000502:physiology* / Q000528:radiation effects; D005239:Fear / Q000502:physiology* / Q000528:radiation effects; D006624:Hippocampus / Q000502:physiology / Q000528:radiation effects; D008027:Light; D008297:Male; D008568:Memory / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008813:Mice, Inbred ICR; D009433:Neural Inhibition / Q000502:physiology / Q000528:radiation effects; D010775:Photic Stimulation / Q000379:methods*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000528:radiation effects; D013569:Synapses / Q000502:physiology* / Q000528:radiation effects
chemical_list: D018091:Receptors, AMPA