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A number of studies have found that contactin-associated protein 2 (Cntnap2) knockout (KO) mice, a well-established mouse model of autism, exhibit reduced interneuron numbers and aberrant phasic inhibition. However, little is known about whether tonic inhibition is disrupted in Cntnap2 KO mice and when the disruption of inhibition begins to occur during postnatal development. We examined tonic and phasic inhibition in layer 2\/3 pyramidal cells of primary visual cortex of Cntnap2 KO at two different developmental stages, three to four and six to eight weeks of age. We found that both phasic inhibition and GABA<jats:sub>A<\/jats:sub>R but not GABA<jats:sub>B<\/jats:sub>R-mediated tonic inhibition was reduced in pyramidal cells from six- to eight-week-old Cntnap2 KO mice, while in three- to four-week-old mice, no significant effects of genotype on tonic or phasic inhibition was observed. We further found that activation of tonic currents mediated by \u03b4-subunit-containing GABA<jats:sub>A<\/jats:sub>Rs reduced neural excitability, an effect that was attenuated by loss of Cntnap2. While the relative contribution of tonic versus phasic inhibition to autism-related symptoms remains unclear, our data suggest that reduced tonic inhibition may play an important role, and \u03b4-subunit-containing GABA<jats:sub>A<\/jats:sub>Rs may be a useful target for therapeutic intervention in autism.<\/jats:p>","DOI":"10.1523\/eneuro.0162-17.2017","type":"journal-article","created":{"date-parts":[[2017,9,16]],"date-time":"2017-09-16T00:25:28Z","timestamp":1505521528000},"page":"ENEURO.0162-17.2017","source":"Crossref","is-referenced-by-count":38,"title":["Developmental Disruption of GABA<sub>A<\/sub>R-Meditated Inhibition in Cntnap2 KO Mice"],"prefix":"10.1523","volume":"4","author":[{"given":"Morgan S.","family":"Bridi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Mi","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2976-5798","authenticated-orcid":false,"given":"Shiyong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"2023041302121486000_4.5.ENEURO.0162-17.2017.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2346"},{"key":"2023041302121486000_4.5.ENEURO.0162-17.2017.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.09.005"},{"key":"2023041302121486000_4.5.ENEURO.0162-17.2017.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.09.015"},{"key":"2023041302121486000_4.5.ENEURO.0162-17.2017.4","doi-asserted-by":"crossref","unstructured":"Bakroon A , Lakshminarayanan V (2016) Visual function in autism spectrum disorders: a critical review. 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