Dsrupting consolidation of fear memory through deep brain stimulation of the medial prefrontal cortex

Abstract

Anxiety disorder poses one of the biggest threat to mental health in the world, yet current therapeutics have been mostly ineffective due to issues with relapse, efficacy, and toxicity of drugs. Deep brain stimulation (DBS) is a promising therapy for treatment-resistant psychiatric disorders including anxiety, despite this, very little is known about the effects of DBS on fear memories. In this study, we used a modified plus-maze discriminative avoidance task to model the interaction between innate fear and conditioned fear. We showed that DBS in the medial prefrontal cortex (mPFC) was able to disrupt consolidation, but not acquisition nor retrieval of fear memories. We validated these results using a standard tone-footshock fear paradigm and showed disruption in both tone and contextual fear memory. We further demonstrated short term, but not long term, changes in dopaminergic receptor expression in the ventral, but not dorsal hippocampus. Similarly, we showed a significant decrease in the immediate early gene c-fos in the ventral but not dorsal hippocampus. Based on our results, we propose a model, using a conceptual artificial neural network, on how neuromodulation is able to disrupt memory. Overall, our data suggest that mPFC stimulation is able to alter fear memories, and should be further studied as a potential therapeutic means for anxiety disorders.