Abstract
A feature of fear memory is its persistence, which could be a factor for affective disorders. Memory retrieval destabilizes consolidated memories, and then rapid molecular cascades contribute to early stabilization of reactivated memories. However, persistence of reactivated memories has been poorly understood. Here, we discover that late Arc (also known as Arg3.1) expression in the mouse basolateral amygdala (BLA) is involved in persistence of newly-acquired and reactivated fear memories. After both fear learning and retrieval, Arc levels increased at 2 h, returned to basal levels at 6 h but increased again at 12 h. Inhibiting late Arc expression impaired memory retention 7 d, but not 2 d, after fear learning and retrieval. Moreover, blockade of NR2B-containing N-methyl-D-aspartate receptors (NMDARs) prevented memory destabilization and inhibited late Arc expression. These findings indicate that NR2B-NMDAR and late Arc expression plays a critical role in the destabilization and persistence of reactivated memories.
Highlights
A feature of fear memory is its persistence, which could be a factor for affective disorders
When mice received infusions of ifenprodil 9 h after retrieval, ifenprodil infusions did not prevent memory impairment resulting from inhibition of late Arc expression (Fig. 3E,F). These results indicate that activation of NR2B-N-methyl-D-aspartate receptors (NMDARs) at the time of memory retrieval is involved in memory destabilization that entails late Arc expression
We found that late Arc expression following fear learning and retrieval is essential for persistence of newly-acquired and reactivated fear memories, respectively
Summary
A feature of fear memory is its persistence, which could be a factor for affective disorders. We discover that late Arc ( known as Arg3.1) expression in the mouse basolateral amygdala (BLA) is involved in persistence of newly-acquired and reactivated fear memories. After both fear learning and retrieval, Arc levels increased at 2 h, returned to basal levels at 6 h but increased again at 12 h. Inhibiting late Arc expression impaired memory retention 7 d, but not 2 d, after fear learning and retrieval. A few recent studies have found that inhibition of brain-derived neurotrophic factor (BDNF) or c-Fos at 12–24 h after learning impairs memory retention at 7 d but not 2 d after learning[8,9,10]. We investigated the mechanisms that prime late Arc expression
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