ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Novel seizure phenotype and sleep disruptions in knock-in mice with hypersensitive alpha 4* nicotinic receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 92 citations in OpenAlex.
- The MA Helix Is Important for Receptor Assembly and Function in the α4β2 nACh Receptor.Membranes · 2023Article
- Mutations of the nACh Receptor M4 Helix Reveal Different Phenotypes in Different Expression Systems: Could Lipids be Responsible?Frontiers in physiology · 2022Article
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Partial and full deletion of nicotinic acetylcholine receptor α4 and β2 subunits reduces sensitivity to acute nicotine administration and development of tolerance following chronic nicotine administration.Behavioural pharmacology · 2020Article
- p53-Sensitive Epileptic Behavior and Inflammation inFrontiers in genetics · 2018Article
- Analgesic, antiallodynic, and anticonvulsant activity of novel hybrid molecules derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide in animal models of pain and epilepsy.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Heterologous expression and nonsense suppression provide insights into agonist behavior at α6β2 nicotinic acetylcholine receptors.Neuropharmacology · 2015Article
- The habenulo-interpeduncular pathway in nicotine aversion and withdrawal.Neuropharmacology · 2015Review
- Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Effectiveness of nicotinic agonists as desensitizers at presynaptic α4β2- and α4α5β2-nicotinic acetylcholine receptors.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2014Article
- The role of the habenula in drug addiction.Frontiers in human neuroscience · 2014Review
- Genetic matters: thirty years of progress using mouse models in nicotinic research.Biochemical pharmacology · 2013Review
- Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2013Article
- A role for α4(non-α6)* nicotinic acetylcholine receptors in motor behavior.Neuropharmacology · 2013Article
- Nicotinic acetylcholine receptors containing the α4 subunit modulate alcohol reward.Biological psychiatry · 2013Article
- Mice expressing the ADNFLE valine 287 leucine mutation of the Β2 nicotinic acetylcholine receptor subunit display increased sensitivity to acute nicotine administration and altered presynaptic nicotinic receptor function.Pharmacology, biochemistry, and behavior · 2013Article
- Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence.Frontiers in psychiatry · 2013Article
- Mammalian sleep genetics.Neurogenetics · 2012Review
- Insights into the neurobiology of the nicotinic cholinergic system and nicotine addiction from mice expressing nicotinic receptors harboring gain-of-function mutations.Pharmacological reviews · 2012Review
- Variations in binding among several agonists at two stoichiometries of the neuronal, α4β2 nicotinic receptor.Journal of the American Chemical Society · 2012Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
A leucine to alanine substitution (L9'A) was introduced in the M2 region of the mouse alpha4 neuronal nicotinic acetylcholine receptor (nAChR) subunit. Expressed in Xenopus oocytes, alpha4(L9'A)beta2 nAChRs were > or =30-fold more sensitive than wild type (WT) to both ACh and nicotine. We generated knock-in mice with the L9'A mutation and studied their cellular responses, seizure phenotype, and sleep-wake cycle. Seizure studies on alpha4-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 alpha4or beta2 subunits. Thalamic cultures and synaptosomes from L9'A mice were hypersensitive to nicotine-induced ion flux. L9'A mice were approximately 15-fold more sensitive to seizures elicited by nicotine injection than their WT littermates. Seizures in L9'A mice differed qualitatively from those in WT: L9'A seizures started earlier, were prevented by nicotine pretreatment, lacked EEG spike-wave discharges, and consisted of fast repetitive movements. Nicotine-induced seizures in L9'A mice were partial, whereas WT seizures were generalized. When L9'A homozygous mice received a 10 mg/kg nicotine injection, there was temporal and phenomenological separation of mutant and WT-like seizures: an initial seizure approximately 20 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'A mice during chronic video/EEG recordings, but their sleep-wake cycle was altered. Our findings show that hypersensitive alpha4* nicotinic receptors in mice mediate changes in the sleep-wake cycle and nicotine-induced seizures resembling ADNFLE.
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Registered trials
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