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As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus. In a separate group of mice, the same population was targeted for transient neuronal silencing with DREADDs. Interneuron ablation produced dramatic seizure clusters and persistent epileptiform activity. Surprisingly, after 1\u2005week seizure activity declined precipitously and persistent epileptiform activity disappeared. Occasional seizures (\u22481\/day) persisted to the end of the experiment at 4\u2005weeks. In contrast to the dramatic impact of interneuron ablation, transient silencing produced large numbers of interictal spikes, a significant but modest increase in seizure occurrence and changes in EEG frequency band power. Taken together, findings suggest that the hippocampus regains relative homeostasis\u2014with occasional breakthrough seizures\u2014in the face of an extensive and abrupt loss of interneurons.<\/jats:p>","DOI":"10.1523\/eneuro.0317-23.2024","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T17:50:17Z","timestamp":1712253017000},"page":"ENEURO.0317-23.2024","source":"Crossref","is-referenced-by-count":10,"title":["Transient Seizure Clusters and Epileptiform Activity Following Widespread Bilateral Hippocampal Interneuron Ablation"],"prefix":"10.1523","volume":"11","author":[{"given":"Mary R.","family":"Dusing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candi L.","family":"LaSarge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin W.","family":"Drake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace C.","family":"Westerkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlie","family":"McCoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby M.","family":"Hetzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly L.","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest V.","family":"Pedapati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4405-2999","authenticated-orcid":false,"given":"Steve C.","family":"Danzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.12.026"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2044"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23147965"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.4","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth762"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.5","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24226"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0429-22.2022"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.7","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14580"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature08002"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046044"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.10.007"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.11","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24011"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.12","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14723"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.13","doi-asserted-by":"publisher","DOI":"10.1038\/nn1499"},{"key":"2024042210552219000_11.4.ENEURO.0317-23.2024.14","unstructured":"Delanerolle N (2012) Histopathology of human epilepsy. 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