Neurobiology of Disease Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive 4* Nicotinic Receptors
نویسندگان
چکیده
Carlos Fonck,1 Bruce N. Cohen,1 Raad Nashmi,1 Paul Whiteaker,3 Daniel A. Wagenaar,2 Nivalda Rodrigues-Pinguet,1 Purnima Deshpande,1 Sheri McKinney,1 Steven Kwoh,1 Jose Munoz,1 Cesar Labarca,1 Allan C. Collins,3 Michael J. Marks,3 and Henry A. Lester1 Divisions of 1Biology and 2Physics, Mathematics, and Astronomy, California Institute of Technology, Pasadena, California 91125, and 3Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, Colorado 80309
منابع مشابه
Behavioral/Systems/Cognitive 4* Nicotinic Receptors in preBötzinger Complex Mediate Cholinergic/Nicotinic Modulation of Respiratory Rhythm
Acetylcholine and nicotine can modulate respiratory patterns by acting on nicotinic acetylcholine receptors (nAChRs) in the preBötzinger complex (preBötC). To further explore the molecular composition of these nAChRs, we studied a knock-in mouse strain with a leucine-to-alanine mutation in the M2 pore-lining region (L9 A) of the nAChR 4 subunit; this mutation renders 4-containing receptors hype...
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This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knock-in mouse strain bearing hypersensitive nicotinic 4 receptor subunits (“L9’S mice”). Adult brains of L9’S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic innervation. Amphetamine-stimulated locomotion is impaired, reflecting a reduction ...
متن کاملPoint mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.
Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by no...
متن کاملIncreased sensitivity to agonist-induced seizures, straub tail, and hippocampal theta rhythm in knock-in mice carrying hypersensitive alpha 4 nicotinic receptors.
We studied a strain of exon replacement mice ("L9'S knock-in") whose alpha4 nicotinic receptor subunits have a leucine to serine mutation in the M2 region, 9' position (Labarca et al., 2001); this mutation renders alpha4-containing receptors hypersensitive to agonists. Nicotine induced seizures at concentrations (1 mg/kg) approximately eight times lower in L9'S than in wild-type (WT) littermate...
متن کاملDemonstration of Functional α4-Containing Nicotinic Receptors in the Medial Habenula
The medial habenula (MHb) exhibits exceptionally high levels of nicotinic acetylcholine receptors (nAChRs), but it remains unclear whether all expressed nAChR subunit mRNAs are translated to form functional receptors. In particular α4 subunits have not been reported to have any functional role, despite strong α4 mRNA expression in the ventrolateral MHb. We studied a strain of knock-in mice expr...
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تاریخ انتشار 2005