{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T19:55:41Z","timestamp":1794513341295,"version":"4.9.1"},"reference-count":39,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T00:00:00Z","timestamp":1448582400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2015,5,27]]},"abstract":"<jats:p>\n                    GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors form Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    permeable channels that mediate the majority of fast synaptic inhibition in the brain. The K\n                    <jats:sup>+<\/jats:sup>\n                    \/Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter KCC2 is the main mechanism by which neurons establish low intracellular Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    levels, which is thought to enable GABAergic inhibitory control of neuronal activity. However, the widely used KCC2 inhibitor furosemide is nonselective with antiseizure efficacy in slices and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , leading to a conflicting scheme of how KCC2 influences GABAergic control of neuronal synchronization. Here we used the selective KCC2 inhibitor VU0463271 [\n                    <jats:italic>N<\/jats:italic>\n                    -cyclopropyl-\n                    <jats:italic>N<\/jats:italic>\n                    -(4-methyl-2-thiazolyl)-2-[(6-phenyl-3-pyridazinyl)thio]acetamide] to investigate the influence of KCC2 function. Application of VU0463271 caused a reversible depolarizing shift in\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    values and increased spiking of cultured hippocampal neurons. Application of VU0463271 to mouse hippocampal slices under low-Mg\n                    <jats:sup>2+<\/jats:sup>\n                    conditions induced unremitting recurrent epileptiform discharges. Finally, microinfusion of VU0463271 alone directly into the mouse dorsal hippocampus rapidly caused epileptiform discharges. Our findings indicated that KCC2 function was a critical inhibitory factor\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.5205-14.2015","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T14:18:15Z","timestamp":1432736295000},"page":"8291-8296","source":"Crossref","is-referenced-by-count":116,"title":["Selective Inhibition of KCC2 Leads to Hyperexcitability and Epileptiform Discharges in Hippocampal Slices and\n                    <i>In Vivo<\/i>"],"prefix":"10.1523","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-0469","authenticated-orcid":false,"given":"Sudhir","family":"Sivakumaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross 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