PT  - JOURNAL ARTICLE
AU  - Daisuke Nakayama
AU  - Hirokazu Iwata
AU  - Chie Teshirogi
AU  - Yuji Ikegaya
AU  - Norio Matsuki
AU  - Hiroshi Nomura
TI  - Long-Delayed Expression of the Immediate Early Gene Arc/Arg3.1 Refines Neuronal Circuits to Perpetuate Fear Memory
AID  - 10.1523/JNEUROSCI.2525-14.2015
DP  - 2015 Jan 14
TA  - The Journal of Neuroscience
PG  - 819--830
VI  - 35
IP  - 2
4099  - http://www.jneurosci.org/content/35/2/819.short
4100  - http://www.jneurosci.org/content/35/2/819.full
SO  - J. Neurosci.2015 Jan 14; 35
AB  - 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.