Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal circuits to perpetuate fear memory.
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.
['Nakayama|Daisuke|D|', 'Iwata|Hirokazu|H|', 'Teshirogi|Chie|C|', 'Ikegaya|Yuji|Y|', 'Matsuki|Norio|N|', 'Nomura|Hiroshi|H|']
D000818:Animals D056547:CA1 Region, Hippocampal D003214:Conditioning, Classical D003598:Cytoskeletal Proteins D049229:Dendritic Spines D005239:Fear D008297:Male D008568:Memory D051379:Mice D008810:Mice, Inbred C57BL D009419:Nerve Tissue Proteins D011930:Reaction Time
Arc/Arg3.1 dendritic spines BDNF fear conditioning hippocampus memory engram