ArticleMolecular psychiatry2011
Altered activity-rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the β2 nicotinic receptor.
Article in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Diverse species of animal models in epilepsy research: Progress and perspectives.Zoological research · 2025Review
- Emerging Role of Tripartite Synaptic Transmission in the Pathomechanism of Autosomal-Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Review
- Tonic-clonic seizures induce hypersomnia and suppress rapid eye movement sleep in mouse models of epilepsy.Sleep advances : a journal of the Sleep Research Society · 2025Article
- Can rodent models elucidate the pathomechanisms of genetic epilepsy?British journal of pharmacology · 2022Review
- Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity.eLife · 2021Article
- Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology.Brain sciences · 2020Review
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- The role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy.Frontiers in physiology · 2015Review
- Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors.Neuron · 2014Article
- Nocturnal frontal lobe epilepsy.Current neurology and neuroscience reports · 2014Review
- Multi-electrode array study of neuronal cultures expressing nicotinic β2-V287L subunits, linked to autosomal dominant nocturnal frontal lobe epilepsy. An in vitro model of spontaneous epilepsy.Frontiers in neural circuits · 2014Article
- Genetic matters: thirty years of progress using mouse models in nicotinic research.Biochemical pharmacology · 2013Review
- B6eGFPChAT mice overexpressing the vesicular acetylcholine transporter exhibit spontaneous hypoactivity and enhanced exploration in novel environments.Brain and behavior · 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
- 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
- Neuronal nicotinic receptors in sleep-related epilepsy: studies in integrative biology.ISRN biochemistry · 2012Review
- Recent advances in gene manipulation and nicotinic acetylcholine receptor biology.Biochemical pharmacology · 2011Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
High-affinity nicotinic receptors containing β2 subunits (β2*) are widely expressed in the brain, modulating many neuronal processes and contributing to neuropathologies such as Alzheimer's disease, Parkinson's disease and epilepsy. Mutations in both the α4 and β2 subunits are associated with a rare partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In this study, we introduced one such human missense mutation into the mouse genome to generate a knock-in strain carrying a valine-to-leucine mutation β2V287L. β2(V287L) mice were viable and born at an expected Mendelian ratio. Surprisingly, mice did not show an overt seizure phenotype; however, homozygous mice did show significant alterations in their activity-rest patterns. This was manifest as an increase in activity during the light cycle suggestive of disturbances in the normal sleep patterns of mice; a parallel phenotype to that found in human ADNFLE patients. Consistent with the role of nicotinic receptors in reward pathways, we found that β2(V287L) mice did not develop a normal proclivity to voluntary wheel running, a model for natural reward. Anxiety-related behaviors were also affected by the V287L mutation. Mutant mice spent more time in the open arms on the elevated plus maze suggesting that they had reduced levels of anxiety. Together, these findings emphasize several important roles of β2* nicotinic receptors in complex biological processes including the activity-rest cycle, natural reward and anxiety.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.