ArticleThe Journal of clinical investigation2024
Stimulation of an entorhinal-hippocampal extinction circuit facilitates fear extinction in a post-traumatic stress disorder model.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The multimodal neuroimaging signatures and gene expression profiles for adverse childhood experiences.BMC medicine · 2025Pooled it
- Gamma entrainment as a functional target in deep brain stimulation.Neural regeneration research · 2026Article
- Top-down medial prefrontal cortex-to-hypothalamic paraventricular nucleus circuit regulates social avoidance and conditioned fear in male mice.Cell discovery · 2026Article
- Circuit-informed modulation of traumatic memory in PTSD: integrating extinction, suppression, and reconsolidation.Molecular psychiatry · 2026Review
- Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group.The American journal of psychiatry · 2026Article
- Deep Brain Stimulation Induces Antidepressant Effects by Restoring High-Fidelity Communication in the BNST-NAc Circuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neuropeptide Y co-opts neuronal ensembles for memory lability and stability.Nature neuroscience · 2026Article
- Progress in spatiotemporal regulation of fear memory: neural circuit mechanisms and implications for PTSD.General psychiatry · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging owing to the fragile nature of fear extinction, for which the ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low-gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed for fear extinction. Gamma entrainment of vCA1 by deep brain stimulation (DBS) or noninvasive transcranial alternating current stimulation (tACS) of LEC persistently enhanced the PV-IN activity in vCA1, thereby promoting fear extinction. These results demonstrate that the LEC-vCA1 pathway forms a top-down motif to empower low-gamma-band oscillations that facilitate fear extinction. Finally, application of low-gamma DBS and tACS to a mouse model with persistent PTSD showed potent efficacy, suggesting that the dedicated LEC-vCA1 pathway can be stimulated for therapy to remove traumatic memory trace.
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