ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Development of a novel analysis method for evaluating PTSD-like behavior in mice based on DSM-V criteria.Stress (Amsterdam, Netherlands) · 2026Article
- Therapeutic hypothermia does not prevent dysmaturity of medial ganglionic eminence-derived interneurons in the dorsal hippocampus after neonatal hypoxia-ischemia.Experimental neurology · 2026Article
- The ventral hippocampus to paraventricular thalamus circuit regulates context-dependent hyperlocomotion through PAC1 receptor signaling in the chronic stress-induced PTSD mouse model.Translational psychiatry · 2026Article
- Synaptic Dysfunction in the Anterior Cingulate Cortex Underlies Pain-Anxiety Comorbidity in a Mandibular Asymmetry Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transcutaneous auricular vagus nerve stimulation alleviates anxiety-like behaviors in mice with post-traumatic stress disorder by regulating glutamatergic neurons in the anterior cingulate cortex.Translational psychiatry · 2025Article
- Single-Nucleus RNA Sequencing Reveals That Gabra6Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell Type-Specific Modulation of Acute Itch Processing in the Anterior Cingulate Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential.Aging and disease · 2024Review
- Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Impaired extinction of fear memory is one of the most common symptoms in post-traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD-ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle-based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD-related impaired extinction of fear memory and provide therapeutic insights into Kv3.2-targeted RNA therapy for PTSD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.