{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:09:18Z","timestamp":1779286158955,"version":"3.51.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401576, 32271076, 2023B1212120004, 82171354"],"award-info":[{"award-number":["82401576, 32271076, 2023B1212120004, 82171354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patients with multiple sclerosis (MS) frequently exhibit hippocampal atrophy and post-traumatic stress disorder (PTSD)\u2013like symptoms, yet the neural mechanisms linking these clinical features remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we employed morphometric analysis, whole-cell recordings, chemogenetic manipulation, and single-nucleus RNA sequencing to investigate the structural, functional, and transcriptional changes in the hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EAE animals recapitulated two core PTSD-relevant phenotypes: impaired fear extinction and contextual fear generalization. Morphometric analysis revealed somatic atrophy of dorsal CA1 pyramidal neurons, and whole-cell recordings demonstrated a marked reduction in firing gain, indicating hippocampal hypoexcitability. Chemogenetic reactivation of CA1 pyramidal neurons ameliorated extinction deficits in EAE mice. Single-nucleus RNA sequencing further revealed a robust neuroimmune-like transcriptional shift in CA1 excitatory neurons, characterized by enrichment of immune\/interferon-associated programs (including antigen processing and presentation and MHC-related pathways) together with apoptosis-related gene signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these data link neuroinflammation-associated neuronal reprogramming to CA1 structural and functional impairment and suggest that restoring hippocampal excitability may represent a therapeutic avenue for MS patients with comorbid PTSD-like symptoms.<\/jats:p>\n                  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