New Experiences Help Strengthen Old Memories

Post by D. Chloe Chung

What's the science?

Long-term memories that are already stored in our brains can be retrieved and reactivated via memory reconsolidation, which is distinct from memory consolidation: encoding recent information into new memory. Several studies have suggested that memory of a weak experience can be strengthened by an associated experience that produces proteins related to plasticity (“behavioral tagging”). Indeed, new experience and information can be simultaneously acquired as pre-existing memories get reactivated, but how new experiences mediate memory reconsolidation is not fully understood. This week in Proceedings of the National Academy of Sciences, Orlandi and colleagues use rat models and multiple behavioral tests to show how memory reconsolidation can be mediated by an accompanying new experience.

How did they do it?

Rats were subject to the weak avoidance test in which they receive an electric foot shock when they step down on the lower platform during the training session. Twenty-four hours later, rats were returned to the test chamber without an electric foot shock as part of the “reactivation session” to retrieve their long-term memory from the earlier training session. The following day, rats were placed in the chamber again and the authors measured how long it took for rats to step down to the lower platform. If rats took a longer time to step down to the platform, they were thought to have a better memory of the foot shock. Different types of inhibitors were given to rats to explore the importance of new protein synthesis and second messenger pathways in memory reconsolidation and behavioral tagging. Also, to introduce a novel experience adjacent to this memory, rats were made to freely explore a new open field in addition to the weak avoidance test. The same experimental scheme was also applied to another assay called the object recognition task to expand understanding of how reconsolidation works for different types of memory. Here, two identical objects were placed in a chamber and one of the two was later moved to a different location. Rats were considered to remember the original locations of objects if they spent more time interacting with the object at a new location.

What did they find?

During the weak avoidance test, rats normally waited for about 2 minutes on average before descending to the lower platform, showing that they possess a long-term memory of the previous electric foot shock. However, rats failed to remember their earlier experience when the new protein synthesis was prevented right after the reactivation session, indicating that proteins related to plasticity are required for memory reconsolidation. Interestingly, forgetfulness was resolved when rats underwent the open field exploration close to the reactivation session (up to 60 minutes before or 30 minutes after the session). This effect disappeared when protein synthesis was inhibited right after the open field exploration, suggesting that a novel experience facilitates memory reconsolidation by providing proteins that could be used to re-solidify pre-existing memories. The authors also tested different protein quinase inhibitors and further dissected that different pathways are responsible for specific aspects of the behavioral tagging process during memory reconsolidation. For the second behavioral test of object recognition, rats showed similar results as they failed to remember the location of objects upon inhibition of protein synthesis, which was resolved by open field exploration (that provides plasticity proteins).

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What’s the impact?

This study presents evidence that behavioral tagging is critical in memory reconsolidation. Specifically, the authors showed that new experiences can contribute to updating old memories by providing newly synthesized proteins that can be used to mediate plasticity. These findings can be potentially useful in developing effective ways to alleviate traumatic memories in individuals who suffer from their negative effects. Conversely, these findings can also help us find ways to strengthen long-term memory for educational purposes.

Orlandi et al. Behavioral tagging underlies memory reconsolidation. PNAS (2020). Access the original scientific publication here.