Deep Brain Stimulation of the Prelimbic Cortex Disrupts Consolidation of Fear Memories

Abstract

Anxiety disorders pose one of the biggest threats to mental health worldwide, yet current therapeutics have been mostly ineffective due to issues with relapse, efficacy, and toxicity. Deep brain stimulation (DBS) is a promising therapy for treatment-resistant psychiatric disorders including anxiety, but very little is known about the effects of DBS on fear memories. In this study, we used a modified plus-maze discriminative task and showed that DBS of the prelimbic cortex was able to disrupt consolidation, but not acquisition or retrieval of avoidance fear memories. These results were further extended to conditioned fear memories using a standard tone-footshock fear conditioning paradigm and we demonstrated that the mechanisms were mediated by dopaminergic modulation and changes of specific neurotransmission and their metabolites in the ventral hippocampus. In conclusion, our study establishes a partial causal role of dopamine 2 receptor on the potential therapeutic role of prelimbic cortex DBS to treat anxiety disorders. Key Points DBS of the PrL was able to disrupt consolidation of fear memories We observed demonstrated short-term changes in dopaminergic receptors, c-Fos expression, and various neurotransmitters and their metabolites in the vHPC We established a partial causal role of dopapmine 2 receptors in the effects