Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of 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 (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC 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 HPC 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 erasure of neural representations that drive pathological fear.
Friday, May 14, 2021
Two promising post-traumatic stress disorder treatments
I want to pass on references to two new approaches to relieving the symptoms of post-traumatic stress disorder (PTSD). Nuwer describes a new study showing that MDMA (known as the party drug Ecstasy, or Molly) can bring relief to PTSD when used in conjunction with talk therapy. Ressler et al. address the problem that human patients cannot be directly re-exposed to trauma-cues of the sort that have been used in animal studies to induce and then disrupt reconsolidation of traumatic memories. They devise a procedure for covertly capturing and attenuating a hippocampu-dependent fear memory in male rats, a procedure that might prove to be useful in human therapy. Here is their abstract: