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Here, we have addressed this question in a reduced model in vitro and have studied the properties and mechanistic involvement of a major class of interneurons, that is, parvalbumin-expressing cells (PVs). When exposed to the KCC2 blocker VU0463271, mouse subicular slices generated hypersynchronous discharges that could be recorded electrophysiologically and visualized as clusters of co-active neurons with calcium imaging. The pharmacological profile of these events resembled interictal-like discharges in human epileptic tissue because of their dependence on GABAA and AMPA receptors. On average, PVs fired before pyramidal cells (PCs) and the area of co-active clusters was comparable to the individual axonal spread of PVs, suggesting their mechanistic involvement. Optogenetic experiments confirmed this hypothesis, as the flash-stimulation of PVs in the presence of VU0463271 initiated interictal-like discharges, whereas their optogenetic silencing suppressed network hyper-excitability. We conclude that reduced KCC2 activity in subicular networks in vitro is sufficient to induce interictal-like activity via altered GABAergic signaling from PVs without other epilepsy-related changes. This conclusion supports an epileptogenic role for impaired subicular KCC2 function during the progression of TLE.<\/jats:p>","DOI":"10.1093\/cercor\/bhab115","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T16:04:18Z","timestamp":1618416258000},"page":"4681-4698","source":"Crossref","is-referenced-by-count":15,"title":["Impaired KCC2 Function Triggers Interictal-Like Activity Driven by Parvalbumin-Expressing Interneurons in the Isolated Subiculum In Vitro"],"prefix":"10.1093","volume":"31","author":[{"given":"Max","family":"Anst\u00f6tz","sequence":"first","affiliation":[{"name":"Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Patrick","family":"Fiske","sequence":"additional","affiliation":[{"name":"Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, 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