Maladaptive memory and fear disorders like post-traumatic stress, anxiety, and phobias are very prevalent in the general population and can be extremely debilitating for those who struggle with them. These disorders are commonly treated with medications and different forms of psychotherapy. In recent years, a focus of investigation pertaining to these disorders has been the process of memory reconsolidation. Memories residing in long term memory cannot be necessarily changed or altered. However, when a memory is retrieved from long term memory into our consciousness and working memory, it is much more malleable and more easily modulated. When the memory is restored into long term memory, this is referred to as memory reconsolidation. This sensitive period is comparable to the state of initial short-term memories. That period has been the target of manipulation in the hopes of developing therapeutic treatments for maladaptive memory disorders. Research has been done to investigate both behavioral and biological interventions (or a combination of both) aimed at disrupting fear memories while they are being reconsolidated as a form of treatment.
In a study titled Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear by Grella et al. (2022) set out to investigate a potential therapeutic invention that disrupts fear memory reconsolidation using optogenetics to activates neurons in the dorsal dentate gyrus (dDG) of the hippocampus. Grella et al. (2022) used the Tet-tag system to label neurons in the dDG that are activated during exposure to positive, negative, or neutral experiences. The researchers then induced the formation of fear memories in mice by using a shock conditioning system. The mice were then given a fear recall test where they were re-exposed to the conditioning environment and stimulus. During the recall test session, blue light was used to activate the tagged neurons in the hippocampus. This optogenetic component occurred either in the first or last 10 minutes of a 20-minute fear recall session. The mice then underwent extinction sessions in the conditioning environment where they received no shock or light stimulation. After the extinction sessions they were re-exposed to the shock stimulus in a different environment and then again in the conditioning environment. During all the shock sessions, the mice’s levels of freezing in response to the shock was recorded. This study found that when positive memories are reactivated during the fear memory reconsolidation, it can reduce the level of fear experienced during subsequent fear memory reconsolidations. Their findings are promising roots of potential treatments for humans with disorders like PTSD and anxiety.
The review paper titled Reconsolidation/Destabilization, extinction and forgetting of memory as therapeutic targets for PTSD by Satoshi Kida discusses how the investigation and discovery of fear mechanisms on the cellular, molecular, and circuit level have facilitated the improvement of PTSD interventions. Kida notes how the strong memories and flashbacks tied to PTSD that people experience repeatedly is theorized to be very hippocampus dependent and never really gets fully consolidated into further out cortical regions. iT is thought to be this way because those who PTSD will experiences the same flashbacks repeatedly, bringing it into their consciousness awareness and working memory repeatedly. Kida mentions how one theorized disruption of the reconsolidation of a memory is the inhibition of gene expression during that reconsolidation. It is also noted how research has shown that memory retrieval does not always lead to the destabilization/reconsolidation of the fear memory and that this can be dependent on the strength and age of the memory. Another past discovery with the potential for treatment applications is the phenomenon of fear memory extinction. Kida discusses how this does not mean a fear memory is erased, but a newly learned and encoded extinction memory suppresses the fear. Another important area of investigation that could be a base of treatment is the active act of forgetting a memory. Kida discusses how the forgetting a hippocampus-dependent memory involves an increase in adult hippocampal neurogenesis which may contribute to the "clearance" of the memory. Kida notes that this could be a potential basis for a treatment of PTSD, but has garnered controversy that must be noted. Kida makes the point that there needs to be an adequate focus on treating older more consolidated memories which have usually been out into the cortex as opposed to directly hippocampus-dependent memories. Using the mechanism of hippocampal neurogeneis would require making older memories hippocampus-dependent once again. Kida concludes the paper by stating how inducing the forgetting of memories may be a sufficient alternative to improve current PTSD treatments and therapies.
The Kida review paper discusses the use of reconsolidation in PTSD research and treatment, similar to the research done in the Grella et al. (2022) Both research paper show the great potential of destabilization/reconsolidation has as a base of different therapies and treatments of PTSD and possibly other disorders that involve maladaptive fear memories. Further research on this neural mechanism could get us closer to developing better supports for the people all over the world who struggle under the weight of maladaptive memory.
Citations
Grella, S. L., Fortin, A. H., Ruesch, E., Bladon, J. H., Reynolds, L. F., Gross, A., . . . Ramirez, S. (2022). Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear. Nature Communications. doi:10.1101/2021.09.16.460695
Satoshi, K. (2018). Reconsolidation/destabilization, extinction and forgetting of Fear memory as therapeutic targets for PTSD. Retrieved December 14, 2022, from https://pubmed.ncbi.nlm.nih.gov/30374892/
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