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However, how diffuse injury differentially alters hippocampal subregions across time remains incompletely defined. Here, we used a mouse closed-head injury model to characterize early transcriptomics, subacute-to-chronic electrophysiology, dendritic spine morphology, and delayed immunoreactivity for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (IBA1), and the pan-leukocyte marker CD45. Bulk RNA sequencing at 9, 24, and 72\u2005h post-injury revealed induction of immediate early genes and neuronal excitability transcripts at 9\u2005h alongside inflammatory pathways. These neuronal signatures diminished by 24\u201372\u2005h while immune-associated programs persisted. Ex vivo field recordings in CA1 and dentate gyrus at 1, 3, and 6 weeks post-injury revealed reductions in synaptic strength in both regions at 1 week. Dentate gyrus deficits persisted at 3 weeks but recovered by 6 weeks, whereas CA1 showed depression at 1 and 6 weeks with relative sparing at 3 weeks. Fibre volley recruitment was preserved across regions and timepoints, arguing against gross presynaptic loss. Population spike thresholds were reduced in both regions, indicating increased neuronal excitability that persisted in CA1 but partially recovered in dentate gyrus. DiOlistic labelling and spine reconstruction revealed stable total spine density, but spine class composition showed sex-dependent injury effects in CA1 with altered mushroom and stubby proportions in males. Immunohistochemistry across 1\u20138 weeks post-injury revealed cortical gliosis but no injury-related changes in hippocampal GFAP or IBA1, while CD45 immunoreactivity increased in a delayed, sex-dependent manner within hippocampus. Together, these findings show that a single closed-head injury produces sustained hippocampal circuit dysfunction characterized by reduced synaptic strength and increased neuronal excitability, with region-dependent recovery dynamics, preserved presynaptic recruitment, and delayed hippocampal CD45 increases that do not parallel local glial activation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag268","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:50:21Z","timestamp":1783684221000},"source":"Crossref","is-referenced-by-count":0,"title":["A single mild closed-head injury disrupts synaptic strength and promotes hippocampal hyperexcitability in mice"],"prefix":"10.1093","volume":"8","author":[{"given":"Jonathan C","family":"Vincent","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Lanning","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Saito","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cate D","family":"Cox","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leke","family":"Bytyqi","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah M","family":"Shepard","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake K","family":"Byer","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret R","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Macheda","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly N","family":"Roberts","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M","family":"Hash","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A","family":"McLaurin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-0049","authenticated-orcid":false,"given":"Josh M","family":"Morganti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4646-6757","authenticated-orcid":false,"given":"Adam D","family":"Bachstetter","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]},{"name":"Sanders-Brown Center on Aging, University of Kentucky , Lexington, KY 40536-0509 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"2026072212171085900_fcag268-B1","volume-title":"Traumatic brain injury: A roadmap for accelerating 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