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We evaluated the effect of recurrent seizure-like events (SLE) on \u03b15\u2013 and \u03b4\u2013GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor (\u03b15- and \u03b4-GABA\n                    <jats:sub>A<\/jats:sub>\n                    R) subunit expression and tonic inhibition in neonatal C57BL\/6J mice (P6\u20139, both sexes) using acute brain slices. We investigated the impact of THIP (gaboxadol) on neonatal behavioral seizures, neuronal apoptosis, and neurodegeneration in vivo. We found neonatal neocortical expression of \u03b15- and \u03b4-GABA\n                    <jats:sub>A<\/jats:sub>\n                    R subunits. Blocking \u03b15-GABA\n                    <jats:sub>A<\/jats:sub>\n                    Rs with L-655,708 did not affect acute neonatal SLE, whereas enhancing \u03b4-GABA\n                    <jats:sub>A<\/jats:sub>\n                    Rs with THDOC, a neurosteroid, reduced them. The \u03b15- and \u03b4-GABA\n                    <jats:sub>A<\/jats:sub>\n                    R membrane expression increased after 8 hours of neonatal SLE and correlated with increased \u03b4-mediated conductance but not \u03b15-mediated conductance. Enhancing tonic inhibition was more effective in reducing recurrent neonatal SLE (8 hours) compared with early treatment. Increasing tonic inhibition reduced the duration, severity, and number of kainic acid\u2013induced in vivo neonatal behavioral seizures without increasing neurodegeneration or apoptosis. We conclude that recurrent neonatal seizures increase tonic inhibition. Therefore, enhancing tonic inhibition may be a treatment strategy for prolonged neonatal status epilepticus.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.196152","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T16:01:06Z","timestamp":1758038466000},"source":"Crossref","is-referenced-by-count":1,"title":["Recurrent neonatal seizures increase tonic inhibition and respond to enhancers of \u03b4-containing GABAA receptors"],"prefix":"10.1172","volume":"10","author":[{"given":"Gage T.","family":"Liddiard","sequence":"first","affiliation":[{"name":"Stead Family Department of Pediatrics,"},{"name":"Interdisciplinary Graduate Program in Neuroscience,"},{"name":"Department of Neurology,"},{"name":"Medical Scientist Training Program, and"},{"name":"Iowa Neuroscience Institute, The University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon 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