Prelimbic Cortical Stimulation Disrupts Fear Memory Consolidation through Ventral Hippocampal Dopamine 2 Receptors.

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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 of the medications. 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 employed a standard tone-footshock fear conditioning paradigm and modified plus maze discriminative avoidance task to probe the effects of Prelimbic Cortex (PrL) DBS on various stages of memory. We identified memory consolidation stage as a critical time point to disrupt fear memory via PrL DBS. The observed disruption was partially modulated by the inactivation of the ventral hippocampus (vHPC) and the transient changes in vHPC dopamine 2 receptors expression upon PrL DBS. We also observed wide-scale changes of various neurotransmitters and their metabolites in vHPC, confirming its important role in response to PrL DBS. These findings highlight the molecular mechanism in the vHPC in response to PrL stimulation, and may have translational value, indicating that targeting the PrL in the memory consolidation stage via non-invasive neuromodulation techniques may be a feasible therapeutic strategy against anxiety disorders.

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Authors: Shawn Zheng Kai Tan, Chi Him Poon, Ying-Shing Chan, Lee Wei Lim