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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\u2010ACC 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\u2010based 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\u2010related impaired extinction of fear memory and provide therapeutic insights into Kv3.2\u2010targeted RNA therapy for PTSD.<\/jats:p>","DOI":"10.1002\/advs.202305939","type":"journal-article","created":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T09:36:30Z","timestamp":1702719390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model"],"prefix":"10.1002","volume":"11","author":[{"given":"Haoxiang","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Neurobiology School of Basic Medicine Fourth Military Medical University  Xi'an 710032 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