Prelimbic cortical stimulation disrupts fear memory consolidation through ventral hippocampal dopamine D₂ receptors

Abstract

Background and Purpose 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 deep brain stimulation on fear memories. Experimental Approach 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 deep brain stimulation on various stages of memory. Key Results We identified memory consolidation stage as a critical time point to disrupt fear memory via prelimbic cortex deep brain stimulation. The observed disruption was partially modulated by the inactivation of the ventral hippocampus and the transient changes in ventral hippocampus dopamine (D2) receptors expression upon prelimbic cortex deep brain stimulation. We also observed wide‐scale changes of various neurotransmitters and their metabolites in ventral hippocampus, confirming its important role in response to prelimbic cortex deep brain stimulation. Conclusion and Implications These findings highlight the molecular mechanism in the ventral hippocampus in response to prelimbic cortex stimulation and may have translational value, indicating that targeting the prelimbic cortex in the memory consolidation stage via non‐invasive neuromodulation techniques may be a feasible therapeutic strategy against anxiety disorders.

Distribution and inter-regional relationship of amyloid-beta plaque deposition in a 5xFAD mouse model of Alzheimer’s disease

“…The cerebral cortex is highly involved in hippocampal-dependent memory formation, given that it receives numerous projections from the hippocampus. The projection from the hippocampus to medial prefrontal cortex regulates social, hippocampal-dependent and fear memory ( Lim et al, 2015a ; Liu et al, 2015 ; Tan et al, 2020a , 2021 ), whereas the projection from hippocampus to the somatosensory cortex regulates somatosensory responses and the consolidation of human motor memory ( Bellistri et al, 2013 ; Kumar et al, 2019 ). Moreover, projections from the hippocampus to other cortical areas, such as the retrosplenial cortex, are involved in the retention of recognition memory ( Balcerek et al, 2021 ).…”

Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression

“…The dorsal hippocampus was dissected to examine the expression levels of neurogenesis-related genes. Real-time PCR was performed according to previously published methodology [ 47 , 48 ]. Total RNA was isolated from the hippocampus using TRIZOL (Life Technologies, Carlsbad, USA) and converted into cDNA using a cDNA synthesis kit (Takara Bio Inc., Shiga, Japan).…”

The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease

“…Recent progress in nanotechnology [ 84 ] and neuromodulation techniques [ 85 , 86 , 87 , 88 , 89 ] could pave the way for revolutionizing the development of compounds to tackle dementia. In particular, one could combine HE treatment with an invasive/non-invasive brain stimulation approach to enhance the therapeutic potential of memory function in AD patients [ 85 , 86 , 87 , 88 , 89 ].…”

“…Recent progress in nanotechnology [ 84 ] and neuromodulation techniques [ 85 , 86 , 87 , 88 , 89 ] could pave the way for revolutionizing the development of compounds to tackle dementia. In particular, one could combine HE treatment with an invasive/non-invasive brain stimulation approach to enhance the therapeutic potential of memory function in AD patients [ 85 , 86 , 87 , 88 , 89 ]. In this respect, the development of nanotherapeutics with multi-functionalities has considerable potential to bridge the gap between the challenges associated with current therapeutics and their clinical application as treatments for AD.…”