title: Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal circuits to perpetuate fear memory.
abstract: Fear memories typically persist for long time periods, and persistent fear memories contribute to post-traumatic stress disorder. However, little is known about the cellular and synaptic mechanisms that perpetuate long-term memories. Here, we find that mouse hippocampal CA1 neurons exhibit biphasic Arc (also known as Arg3.1) elevations after fear experience and that the late Arc expression regulates the perpetuation of fear memoires. An early Arc increase returned to the baseline after 6 h, followed by a second Arc increase after 12 h in the same neuronal subpopulation; these elevations occurred via distinct mechanisms. Antisense-induced blockade of late Arc expression disrupted memory persistence but not formation. Moreover, prolonged fear memories were associated with the delayed, specific elimination of dendritic spines and the reactivation of neuronal ensembles formed during fear experience, both of which required late Arc expression. We propose that late Arc expression refines functional circuits in a delayed fashion to prolong fear memory.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakayama
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, and.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, and.
authors.forename: Chie
authors.initials: C
authors.lastname: Teshirogi
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, and Center for Information and Neural Networks, Suita City, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikegaya
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, and.
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan, and nomura@mol.f.u-tokyo.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nomura
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D003214:Conditioning, Classical; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D005239:Fear; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011930:Reaction Time
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein
keywords: Arc/Arg3.1; BDNF; dendritic spines; fear conditioning; hippocampus; memory engram