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In the early stages of Alzheimer's disease, vulnerable circuits in the temporal lobe exhibit diminished activity prior to overt degeneration. It remains unclear whether these functional changes contribute to regional vulnerability or are simply a consequence of pathology. We previously found that entorhinal neurons in the temporal cortex undergo cell death following transient suppression of electrical activity, suggesting a causal role for activity disruption in neurodegeneration. Here we demonstrate that electrical arrest of this circuit stimulates the injury\u2010response transcription factor c\u2010Jun. Entorhinal silencing induces transcriptional changes consistent with c\u2010Jun activation that share characteristics of gene signatures in other neuronal populations vulnerable to Alzheimer's disease. Despite its established role in the neuronal injury response, inhibiting c\u2010Jun failed to ameliorate entorhinal degeneration following activity disruption. Finally, we present preliminary evidence of integrated stress response activity that may serve as an alternative hypothesis to what drives entorhinal degeneration after silencing. Our data demonstrate that c\u2010Jun is activated in response to neuronal silencing in the entorhinal cortex but is decoupled from subsequent neurodegeneration.<\/jats:p>","DOI":"10.1111\/ejn.16575","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:18:45Z","timestamp":1729815525000},"page":"6704-6719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemogenetic neuronal silencing decouples c\u2010Jun activation from cell death in the temporal cortex"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3320-0485","authenticated-orcid":false,"given":"Caleb A.","family":"Wood","sequence":"first","affiliation":[{"name":"Department of Neuroscience Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preethi","family":"Somasundaram","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Dundee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Rudy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent A.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Neurosurgery Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna L.","family":"Jankowsky","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Baylor College of Medicine  Houston Texas USA"},{"name":"Department of Neurosurgery Baylor College of Medicine  Houston Texas USA"},{"name":"Departments of Neurology and Molecular and Cellular Biology, Huffington Center on Aging Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.2.967"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.10.027"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251194298"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700409"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03037.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_2_11_9_1","unstructured":"ChiPlot. 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