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In this study, we investigated the impact of PPT1 deficiency on hippocampal GABAergic interneurons (INs) and associated neural network oscillations in a PPT1-KI (\n                    <jats:italic>CLN1<\/jats:italic>\n                    c.451\u2009C\u2009&gt;\u2009T (p.R151X)) mouse model. Using a combination of in vivo electrophysiology, immunostaining, and fiber photometry, we observed that PPT1 deficiency led to the activation of caspase 3 in parvalbumin-positive (PV\n                    <jats:sup>+<\/jats:sup>\n                    ) INs, an increased activity of pyramidal neurons and theta\/gamma oscillation power, and the disruption of theta-gamma cross-frequency coupling (CFC) in the early stage of the\n                    <jats:italic>CLN1<\/jats:italic>\n                    disease model. In the late stage of the\n                    <jats:italic>CLN1<\/jats:italic>\n                    disease model, we observed the reduced neuronal activity, extensive neuronal loss including PV\n                    <jats:sup>+<\/jats:sup>\n                    INs, and the emergence of spontaneous epileptiform discharges and the pathological ripples. Treatment with diazepam partially restored oscillatory coupling and reduced seizure-like activities. Our research indicated that PPT1 deficiency leads to early selective impairment of PV\n                    <jats:sup>+<\/jats:sup>\n                    INs, triggering overactivation of pyramidal neurons and network dysfunction, which consequently results in seizures and neurodegeneration. This research provides novel insights into the pathogenesis of\n                    <jats:italic>CLN1<\/jats:italic>\n                    disease and potential therapeutic strategies for the intervention of\n                    <jats:italic>CLN1<\/jats:italic>\n                    disease by improving the function of inhibitory INs via caspase inhibition.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-03843-8","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:43:15Z","timestamp":1770014595000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysfunction of GABAergic interneurons underlies altered neural network oscillations associated with epileptiform activity in PPT1-deficient mice"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1835-7385","authenticated-orcid":false,"given":"Jia","family":"Tong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weizhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huifang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanliu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-246X","authenticated-orcid":false,"given":"Wenqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9074-4430","authenticated-orcid":false,"given":"Chengbiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"3843_CR1","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1016\/j.bbamem.2011.07.009","volume":"1808","author":"C Aicart-Ramos","year":"2011","unstructured":"Aicart-Ramos C, Valero RA, Rodriguez-Crespo I. 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