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We generated knock-in mice with the L9\u2032A mutation and studied their cellular responses, seizure phenotype, and sleep-wake cycle. Seizure studies on \u03b14-mutated animals are relevant to epilepsy research because all known mutations linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) occur in the M2 region of \u03b14or \u03b22 subunits. Thalamic cultures and synaptosomes from L9\u2032A mice were hypersensitive to nicotine-induced ion flux. L9\u2032A mice were \u223c15-fold more sensitive to seizures elicited by nicotine injection than their WT littermates. Seizures in L9\u2032A mice differed qualitatively from those in WT: L9\u2032A seizures started earlier, were prevented by nicotine pretreatment, lacked EEG spike-wave discharges, and consisted of fast repetitive movements. Nicotine-induced seizures in L9\u2032A mice were partial, whereas WT seizures were generalized. When L9\u2032A homozygous mice received a 10 mg\/kg nicotine injection, there was temporal and phenomenological separation of mutant and WT-like seizures: an initial seizure \u223c20 s after injection was clonic and showed no EEG changes. A second seizure began 3-4 min after injection, was tonic-clonic, and had EEG spike-wave activity. No spontaneous seizures were detected in L9\u2032A mice during chronic video\/EEG recordings, but their sleep-wake cycle was altered. Our findings show that hypersensitive \u03b14<jats:sup>*<\/jats:sup>nicotinic receptors in mice mediate changes in the sleep-wake cycle and nicotine-induced seizures resembling ADNFLE.<\/jats:p>","DOI":"10.1523\/jneurosci.3597-05.2005","type":"journal-article","created":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T18:02:49Z","timestamp":1133978569000},"page":"11396-11411","source":"Crossref","is-referenced-by-count":84,"title":["Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive \u03b14<sup>*<\/sup>Nicotinic Receptors"],"prefix":"10.1523","volume":"25","author":[{"given":"Carlos","family":"Fonck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce N.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raad","family":"Nashmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Whiteaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Wagenaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivalda","family":"Rodrigues-Pinguet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purnima","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri","family":"McKinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kwoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Munoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Labarca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan C.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry A.","family":"Lester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"2023041303155950000_25.49.11396.1","doi-asserted-by":"crossref","unstructured":"Ashcroft FM (2000) Ion channels and disease: channelopathies. 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