Covert capture and attenuation of a hippocampus-dependent fear memory

Abstract

Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used to safely retrieve traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward conditioning procedure to indirectly retrieve and manipulate a hippocampus-dependent contextual fear engram in male rats. We show that conditioned freezing to a backward conditioned stimulus is mediated by fear to the conditioning context, activates hippocampal ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate hippocampal ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasing neural representations that drive pathological fear.

Neural reinstatement reveals divided organization of fear and extinction memories in the human brain

“…This design may be applied to future work in humans seeking to assess the efficacy of protocols that enhance extinction 77 or modify the underlying fear memory trace through reconsolidation updating. 78 A further possibility to extend this work is to target engagement of activity patterns unique to formation of an extinction memory in distributed networks through closed-loop decoded neurofeedback 79,80 to create an enduring memory of safety. In this way, more precise localization of networks involved in organizing fear and extinction memory could ultimately lead to better treatments of psychiatric disorders like PTSD.…”

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

“…In addition to its expression in mouse brain cell lines, we also identified IL-22Rα expression in the hippocampus and cerebellum of C57BL/6 mice ( Figure 1 D). The hippocampus plays an important role in spatial memory and cognition, enabling information integration and transition from short-term memory to long-term memory [ 25 , 35 , 46 ]. In addition, the cerebellum is involved in motor control [ 32 , 47 , 48 ].…”

Modulating amygdala activation to traumatic memories with a single ketamine infusion

“…Some studies have demonstrated the relevance of dorsal amygdala-hippocampus connectivity in contextual fear memory 11,14 , with some associating the level of amygdala -hippocampus connectivity to the long term retention of fear learning 15 . In a recent study, Ressler and colleagues showed that the hippocampus was involved in contextual fear memory and that inhibition of protein synthesis in hippocampal ensemble disrupted the reconsolidation of fear memories 52 . The authors argue that these findings might help us better understand real-life traumatic memories (which we study here).…”