The Discovery of How the Reactivation of Hippocampal-Mediated Memories can Disrupt Fear During the Reconsolidation Process

    Memories are held in the brain as units activated during times of learning and then brought back to the forefront during a retrieval event (Grella et al 2022). Memory reactivation can lead to memory-updating by activating a small number of specific neurons (Grella et al 2022). Dr. Grella and her associates took the concept of memory retrieval and investigated the idea of interrupting fear memories. They used Tet-tag systems to label neurons in the dorsal dentate gyrus of mice once they were activated by negative, positive, neutral experiences using channelrhodopsin-2 as a marker (Grella et al 2022). The cells were then reactivated artificially in the mice in order to induce “fear memory recall” and open the option for the event of a memory update (Grella et al 2022).

    Researchers found that showing a positive memory while activating the previously tagged cells can cause an update to occur, leading to a reduction in the conditioned response (Grella et al 2022). This is proven further by the positive responses displayed by the mice following the update. With this, they further tested the outcome of triggering a large amount of the marked neurons in the dorsal dentate gyrus, leading to the discovery of another avenue in inducing reconsolidation (Grella et al 2022). They concluded that the behaviors shown when activating the cells in the dorsal dentate gyrus indicates that this brain region can be used in therapeutic treatment for editing memory to suppress fear in instances of anxiety or PTSD (Grella et al 2022).

    Research into the reduction of anxious behaviors takes a different path in psychologist Dr. Eckstein’s lab, where they look to the amygdala. More specifically, how does this known fear center react in the presence of oxytocin. Her and her team’s experiments consisted of displaying a neutral stimulus with an added associated electric shock (Eckstein et al 2014). Participants were selected for an “intranasal dose” of oxytocin or a placebo following the activity (Eckstein et al 2014). They were then shown these same stimuli without the expected shock while being monitored in an MRI machine, in order to measure the activity during the fear extinction therapy (Eckstein et al 2014). Results showed that those who received the dose of oxytocin showed higher activity in the frontal cortex and decreased amygdala response (Eckstein et al 2014). This was an indication of the fear reduction process at work, providing promising evidence supporting the effectiveness of a single dose of oxytocin (Eckstein et al 2014).

    With disorders like anxiety and PTSD plaguing the ones we know and love, the push for some relief is growing. With every case unique, it is important to approach the problem from multiple angles. The first article was able to demonstrate how the stimulation of a specific brain region using channelrhodopsin-2 as a guide can be used to suppress fear memory through the process of memory updating. The idea of using our bodies natural reconsolidation and update method follows a similar path of using a normally naturally occurring hormone to activate the brain’s natural fear suppression region. Small doses of oxytocin show another avenue in using a region’s natural system to be able to regulate the hyperactivity of a fear response. The second article was able to provide evidence of a hormone that dampened the effects of the overactivation of the amygdala. While many may struggle with an unnatural occurrence of a stimulus response, there is promise of science providing ways to keep the activity at bay.

 

References

Grella, S.L., Fortin, A.H., Ruesch, E. et al. Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear. Nat Commun 13, 4733 (2022). https://doi.org/10.1038/s41467-022-32246-8

Eckstein M, Becker B, Scheele D, et al. Oxytocin facilitates the extinction of conditioned fear in humans. Biological Psychiatry. 2015 Aug;78(3):194-202. DOI: 10.1016/j.biopsych.2014.10.015. PMID: 25542304.