Abstract
Learning to avoid threats in the environment is highly adaptive. However, sometimes a dysregulation of fear memories processing may underlie fear-related disorders. Despite recent advances, a major question of how to effectively attenuate persistent fear memories in a safe manner remains unresolved. Here we show experiments employing a behavioural tool to target a specific time window after training to limit the persistence of a fear memory in rats. We observed that exposure to a novel environment 11 h after an inhibitory avoidance (IA) training that induces a long-lasting memory, attenuates the durability of IA memory but not its formation. This effect is time-restricted and not seen when the environment is familiar. In addition, novelty-induced attenuation of IA memory durability is prevented by the intrahippocampal infusion of the CaMKs inhibitor KN-93. This new behavioural approach which targets a specific time window during late memory consolidation, might represent a new tool for reducing the durability of persistent fear memories.
Highlights
When an independent group of animals was tested 7 days after inhibitory avoidance (IA) training we found an impairment in memory retention (Fig. 1b, p < 0.05 in comparison to the Control IA-trained group of rats that were not exposed to open field (OF); Student’s t test, n = 10–12)
This effect was observed during a critical time window after training because no altered retention scores were seen when IA-trained rats were exposed to a novel environment 8 or 23 h after training and tested 2 or 7 days thereafter (Fig. 2)
These findings indicate that exposure to a novel environment late after training selectively attenuates, in a time-dependent manner, the persistence of IA LTM storage without altering memory formation
Summary
These findings indicate that exposure to a novel environment late after training selectively attenuates, in a time-dependent manner, the persistence of IA LTM storage without altering memory formation. Animals were exposed again to the square OF (Fam OF group) or to a round shape novel OF (New OF group) 11 h after IA training and tested for memory retention 7 days after.
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