Gene Symbol: Chrna4
Description: cholinergic receptor, nicotinic, alpha polypeptide 4
Alias: Acra-4, Acra4, EBN1, ENFL1, neuronal acetylcholine receptor subunit alpha-4, a4 nicotinic receptor, acetylcholine receptor alpha 4 neural, acetylcholine receptor, neuronal, nicotinic, alpha-4 subunit, alpha4 nAChR
Species: mouse
Products:     Chrna4

Top Publications

  1. Nashmi R, Xiao C, Deshpande P, McKinney S, Grady S, Whiteaker P, et al. Chronic nicotine cell specifically upregulates functional alpha 4* nicotinic receptors: basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path. J Neurosci. 2007;27:8202-18 pubmed
  2. Whiteaker P, Cooper J, Salminen O, Marks M, McClure Begley T, Brown R, et al. Immunolabeling demonstrates the interdependence of mouse brain alpha4 and beta2 nicotinic acetylcholine receptor subunit expression. J Comp Neurol. 2006;499:1016-38 pubmed
    ..Consequently, it seems that the two subunits' effects on each other's expression are mediated at the protein, rather than gene expression level. ..
  3. Wong J, Ross S, McColl C, Massalas J, Powney E, Finkelstein D, et al. Proconvulsant-induced seizures in alpha(4) nicotinic acetylcholine receptor subunit knockout mice. Neuropharmacology. 2002;43:55-64 pubmed
    ..The results show that a functional deletion of the alpha(4) nAChR subunit in vivo is associated with a major increase in sensitivity to GABA receptor blockers. ..
  4. Schneider A, Atluri P, Shen Q, Barnes W, Mah S, Stadfelt D, et al. Functional nicotinic acetylcholine receptor expression on stem and progenitor cells of the early embryonic nervous system. Ann N Y Acad Sci. 2002;971:135-8 pubmed
    ..We now report the first evidence of functional nicotinic ACh receptors on stem and progenitor cells of fetal mouse cerebral cortex as early as embryonic day 10. ..
  5. Yu W, Guan Z, Nordberg A. Postnatal upregulation of alpha4 and alpha3 nicotinic receptor subunits in the brain of alpha7 nicotinic receptor-deficient mice. Neuroscience. 2007;146:1618-28 pubmed
    ..These data suggest that increased levels of alpha4, alpha3-containing nAChRs, co-assembled with the alpha5 nAChR subunit, may contribute to the normal brain development of alpha7 -/- and alpha7 +/- mice. ..
  6. Exley R, Maubourguet N, David V, Eddine R, Evrard A, Pons S, et al. Distinct contributions of nicotinic acetylcholine receptor subunit alpha4 and subunit alpha6 to the reinforcing effects of nicotine. Proc Natl Acad Sci U S A. 2011;108:7577-82 pubmed publisher
  7. Tapper A, McKinney S, Nashmi R, Schwarz J, Deshpande P, Labarca C, et al. Nicotine activation of alpha4* receptors: sufficient for reward, tolerance, and sensitization. Science. 2004;306:1029-32 pubmed
    ..These data indicate that activation of a4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization. ..
  8. Hendrickson L, Zhao Shea R, Pang X, Gardner P, Tapper A. Activation of alpha4* nAChRs is necessary and sufficient for varenicline-induced reduction of alcohol consumption. J Neurosci. 2010;30:10169-76 pubmed publisher
    ..Together, our data indicate that activation of alpha4* nAChRs is necessary and sufficient for varenicline reduction of alcohol consumption. ..
  9. Champtiaux N, Gotti C, Cordero Erausquin M, David D, Przybylski C, Léna C, et al. Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J Neurosci. 2003;23:7820-9 pubmed

More Information


  1. McGranahan T, Patzlaff N, Grady S, Heinemann S, Booker T. ?4?2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief. J Neurosci. 2011;31:10891-902 pubmed publisher
    ..This is the first work to develop a dopaminergic specific deletion of a nAChR subunit and examine resulting changes in nicotine-related behaviors. ..
  2. Klink R, de Kerchove d Exaerde A, Zoli M, Changeux J. Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci. 2001;21:1452-63 pubmed
    ..Neurons in the DA nuclei thus exhibit a diversity of nAChRs that might differentially modulate reinforcement and motor behavior. ..
  3. Wilking J, Hesterberg K, Crouch E, Homanics G, Stitzel J. Chrna4 A529 knock-in mice exhibit altered nicotine sensitivity. Pharmacogenet Genomics. 2010;20:121-30 pubmed publisher genetic variant has been implicated in altering nicotine sensitivity in mice is a T529A polymorphism in Chrna4, the gene that encodes the nicotinic receptor (nAChR) alpha4 subunit...
  4. Fonck C, Nashmi R, Salas R, Zhou C, Huang Q, De Biasi M, et al. Demonstration of functional alpha4-containing nicotinic receptors in the medial habenula. Neuropharmacology. 2009;56:247-53 pubmed publisher
    ..Thus alpha4* nAChRs contribute to the selective activation of a subset of MHb neurons. Subunit composition analysis based on gain-of-function knock-in mice provides a useful experimental paradigm. ..
  5. Drenan R, Grady S, Steele A, McKinney S, Patzlaff N, McIntosh J, et al. Cholinergic modulation of locomotion and striatal dopamine release is mediated by alpha6alpha4* nicotinic acetylcholine receptors. J Neurosci. 2010;30:9877-89 pubmed publisher
    ..These results implicate alpha6alpha4beta2* nAChRs in cholinergic control of DA transmission, and strongly suggest that these receptors are candidate drug targets for disorders involving the DA system...
  6. McClure Begley T, Grady S, Marks M, Collins A, Stitzel J. Presynaptic GABAB autoreceptor regulation of nicotinic acetylcholine receptor mediated [(3)H]-GABA release from mouse synaptosomes. Biochem Pharmacol. 2014;91:87-96 pubmed publisher
    ..In addition, the functional modulation of ?4?2*-type nAChRs on striatal GABAergic nerve terminals by GABAB autoreceptor activation is time-sensitive and appears to involve opposing actions of calcineurin and PKC. ..
  7. Orb S, Wieacker J, Labarca C, Fonck C, Lester H, Schwarz J. Knockin mice with Leu9'Ser alpha4-nicotinic receptors: substantia nigra dopaminergic neurons are hypersensitive to agonist and lost postnatally. Physiol Genomics. 2004;18:299-307 pubmed
    ..This novel concept may be relevant to the pathophysiology of Parkinson disease. ..
  8. Takarada T, Nakamichi N, Kitajima S, Fukumori R, Nakazato R, Le N, et al. Promoted neuronal differentiation after activation of alpha4/beta2 nicotinic acetylcholine receptors in undifferentiated neural progenitors. PLoS ONE. 2012;7:e46177 pubmed publisher
  9. Garção P, Oliveira C, Cunha R, Agostinho P. Subsynaptic localization of nicotinic acetylcholine receptor subunits: a comparative study in the mouse and rat striatum. Neurosci Lett. 2014;566:106-10 pubmed publisher
  10. Svedberg M, Svensson A, Johnson M, Lee M, Cohen O, Court J, et al. Upregulation of neuronal nicotinic receptor subunits alpha4, beta2, and alpha7 in transgenic mice overexpressing human acetylcholinesterase. J Mol Neurosci. 2002;18:211-22 pubmed
  11. Fonck C, Nashmi R, Deshpande P, Damaj M, Marks M, Riedel A, et al. Increased sensitivity to agonist-induced seizures, straub tail, and hippocampal theta rhythm in knock-in mice carrying hypersensitive alpha 4 nicotinic receptors. J Neurosci. 2003;23:2582-90 pubmed
    ..These data support the possible involvement of gain-of-function alpha4 receptors in autosomal dominant nocturnal frontal-lobe epilepsy. ..
  12. Jeanclos E, Lin L, Treuil M, Rao J, DeCoster M, Anand R. The chaperone protein 14-3-3eta interacts with the nicotinic acetylcholine receptor alpha 4 subunit. Evidence for a dynamic role in subunit stabilization. J Biol Chem. 2001;276:28281-90 pubmed
    ..14-3-3 coimmunopurified with native alpha4 AChRs from brain. These results support a role for 14-3-3 in dynamically regulating the expression levels of alpha4beta2 AChRs through its interaction with the alpha4 subunit. ..
  13. Stitzel J. Naturally occurring genetic variability in the nicotinic acetylcholine receptor alpha4 and alpha7 subunit genes and phenotypic diversity in humans and mice. Front Biosci. 2008;13:477-91 pubmed
  14. Chambers D, Peters J, Abbott C. The lethal mutation of the mouse wasted (wst) is a deletion that abolishes expression of a tissue-specific isoform of translation elongation factor 1alpha, encoded by the Eef1a2 gene. Proc Natl Acad Sci U S A. 1998;95:4463-8 pubmed
    ..These data suggest that there are tissue-specific forms of the translation elongation apparatus essential for postnatal survival in the mouse. ..
  15. Aracri P, Meneghini S, Coatti A, Amadeo A, Becchetti A. ?4?2? nicotinic receptors stimulate GABA release onto fast-spiking cells in layer V of mouse prefrontal (Fr2) cortex. Neuroscience. 2017;340:48-61 pubmed publisher
    ..These mechanisms may contribute to the nAChR-dependent stimulation of excitability during cognitive tasks as well as to the hyperexcitability caused by hyperfunctional heteromeric nAChRs in sleep-related epilepsy. ..
  16. Shao X, Tan W, Xiu J, Puskar N, Fonck C, Lester H, et al. Alpha4* nicotinic receptors in preBotzinger complex mediate cholinergic/nicotinic modulation of respiratory rhythm. J Neurosci. 2008;28:519-28 pubmed publisher
    ..Furthermore, functional alpha4* nAChRs are present in XII nucleus and mediate cholinergic/nicotinic modulation of tonic activity in XIIn. ..
  17. Cordero Erausquin M, Changeux J. Tonic nicotinic modulation of serotoninergic transmission in the spinal cord. Proc Natl Acad Sci U S A. 2001;98:2803-7 pubmed
    ..In addition, the presence of a tonic nicotinic modulation of 5-HT release indicates that endogenous acetylcholine plays a role in the physiological regulation of descending 5-HT pathways to the spinal cord. ..
  18. Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak M, Fonck C, et al. Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety. Proc Natl Acad Sci U S A. 2001;98:2786-91 pubmed
    ..These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease. ..
  19. Schwarz J, Schwarz S, Dorigo O, Stützer A, Wegner F, Labarca C, et al. Enhanced expression of hypersensitive alpha4* nAChR in adult mice increases the loss of midbrain dopaminergic neurons. FASEB J. 2006;20:935-46 pubmed
    ..This produced increased L9'S mutant nAChR expression, which in turn led to nicotinic cholinergic excitotoxicity in dopaminergic neurons. ..
  20. Mousavi M, Hellström Lindahl E. Nicotinic receptor agonists and antagonists increase sAPPalpha secretion and decrease Abeta levels in vitro. Neurochem Int. 2009;54:237-44 pubmed publisher
    ..Nicotinic drugs directed towards specific nAChR subtypes might therefore be beneficial for the treatment of AD not only by lowering Abeta production but also by enhance release of neuroprotective sAPPalpha. ..
  21. Yang Y, Beyer B, Otto J, O Brien T, Letts V, White H, et al. Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold. Hum Mol Genet. 2003;12:975-84 pubmed
    ..Two of these genes, Kcnq2 and Chrna4, are known to be mutated in human epilepsy families...
  22. Wildeboer K, Stevens K. Stimulation of the alpha4beta2 nicotinic receptor by 5-I A-85380 improves auditory gating in DBA/2 mice. Brain Res. 2008;1224:29-36 pubmed publisher
    ..Thus, the present study implicates the involvement of more than one subtype of nAChR in the auditory gating of DBA/2 mice, specifically the alpha4beta2 nAChR, and its role in the response amplitude to the first stimulus. ..
  23. Kim H, Flanagin B, Qin C, Macdonald R, Stitzel J. The mouse Chrna4 A529T polymorphism alters the ratio of high to low affinity alpha 4 beta 2 nAChRs. Neuropharmacology. 2003;45:345-54 pubmed
    Previously, a missense polymorphism was identified in the mouse nicotinic receptor alpha4 subunit gene, Chrna4. This polymorphism leads to an Ala/Thr variation at amino acid position 529 of the alpha4 subunit...
  24. O Hara B, Macdonald E, Clegg D, Wiler S, Andretic R, Cao V, et al. Developmental changes in nicotinic receptor mRNAs and responses to nicotine in the suprachiasmatic nucleus and other brain regions. Brain Res Mol Brain Res. 1999;66:71-82 pubmed
    ..In particular, a small 1.4 kb alpha2-related mRNA is highly expressed during early development, perhaps indicating an important novel function for this subunit. ..
  25. Renda A, Nashmi R. Chronic nicotine pretreatment is sufficient to upregulate ?4* nicotinic receptors and increase oral nicotine self-administration in mice. BMC Neurosci. 2014;15:89 pubmed publisher
    ..Chronic forced pre-exposure of nicotine is sufficient to induce elevated oral nicotine intake and supports the postulate that nAChR upregulation may be a key factor influencing nicotine self-administration. ..
  26. Exley R, McIntosh J, Marks M, Maskos U, Cragg S. Striatal ?5 nicotinic receptor subunit regulates dopamine transmission in dorsal striatum. J Neurosci. 2012;32:2352-6 pubmed publisher
  27. Dehkordi O, Millis R, Dennis G, Coleman B, Johnson S, Changizi L, et al. Alpha-7 and alpha-4 nicotinic receptor subunit immunoreactivity in genioglossus muscle motoneurons. Respir Physiol Neurobiol. 2005;145:153-61 pubmed
    ..90% in rostral areas (P=0.074). These results demonstrate that nAChR immunoreactivity is present in genioglossal motoneurons and suggest a role for alpha-7 and alpha-4 subunits containing nAChRs in the regulation of upper airway patency. ..
  28. Meyer E, Yoshikami D, McIntosh J. The neuronal nicotinic acetylcholine receptors alpha 4* and alpha 6* differentially modulate dopamine release in mouse striatal slices. J Neurochem. 2008;105:1761-9 pubmed publisher
    ..These results indicate that there are different classes of striatal DA-ergic fibers that express different subtypes of nicotinic receptors. ..
  29. Nordman J, Muldoon P, Clark S, Damaj M, Kabbani N. The ?4 nicotinic receptor promotes CD4+ T-cell proliferation and a helper T-cell immune response. Mol Pharmacol. 2014;85:50-61 pubmed publisher
    ..We thus present a new mechanism of ?4 nAChR signaling and immune regulation in T cells, possibly accounting for the effect of smoking on the immune system. ..
  30. Dougherty J, Wu J, Mehta T, Brown B, Nichols R. Chronic nicotine alters nicotinic receptor-induced presynaptic Ca2+ responses in isolated nerve terminals. Neurochem Res. 2008;33:1106-12 pubmed
    ..These findings suggest that chronic exposure to nicotine may lead to enhanced sensitivity to nicotine at select presynaptic sites in brain via up-regulation of high-affinity nicotinic receptors. ..
  31. Li Y, LaCroix C, Freeling J. Specific subtypes of nicotinic cholinergic receptors involved in sympathetic and parasympathetic cardiovascular responses. Neurosci Lett. 2009;462:20-3 pubmed publisher
    ..These data suggest that specific subtypes of nicotinic receptors at the level of the ganglia may play distinct roles in mediating sympathetic or parasympathetic activation. ..
  32. Nagavarapu U, Boyd R. Distribution of neuronal nicotinic acetylcholine receptor gene restriction fragment length polymorphisms in inbred and partially inbred mice. Pharmacogenetics. 1995;5:326-31 pubmed
  33. Arora K, Cheng J, Nichols R. Nicotinic Acetylcholine Receptors Sensitize a MAPK-linked Toxicity Pathway on Prolonged Exposure to β-Amyloid. J Biol Chem. 2015;290:21409-20 pubmed publisher
  34. Peng C, Engle S, Yan Y, Weera M, Berry J, Arvin M, et al. Altered nicotine reward-associated behavior following ?4 nAChR subunit deletion in ventral midbrain. PLoS ONE. 2017;12:e0182142 pubmed publisher
    ..These results reveal that attenuation of ?4* nAChR function in reward-related brain circuitry of adult animals may increase nicotine intake by enhancing the rewarding effects and/or reducing the aversive effects of nicotine. ..
  35. Soll L, Grady S, Salminen O, Marks M, Tapper A. A role for ?4(non-?6)* nicotinic acetylcholine receptors in motor behavior. Neuropharmacology. 2013;73:19-30 pubmed publisher
    ..Together, these data indicate that ?4(non-?6)* nAChR have an impact on motor output and may be potential molecular targets for treatment of disorders associated with motor impairment. ..
  36. Ritzenthaler J, Roser Page S, Guidot D, Roman J. Nicotinic acetylcholine receptors are sensors for ethanol in lung fibroblasts. Alcohol Clin Exp Res. 2013;37:914-23 pubmed publisher
  37. Ibanez Tallon I, Miwa J, Wang H, Adams N, Crabtree G, Sine S, et al. Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1. Neuron. 2002;33:893-903 pubmed
  38. Dobelis P, Marks M, Whiteaker P, Balogh S, Collins A, Stitzel J. A polymorphism in the mouse neuronal alpha4 nicotinic receptor subunit results in an alteration in receptor function. Mol Pharmacol. 2002;62:334-42 pubmed
    ..The potential role of a single nucleotide polymorphism (SNP) in the nicotinic receptor alpha4 subunit gene (Chrna4) on nicotinic receptor binding and function in mice was also evaluated...
  39. Rossi F, Pizzorusso T, Porciatti V, Marubio L, Maffei L, Changeux J. Requirement of the nicotinic acetylcholine receptor beta 2 subunit for the anatomical and functional development of the visual system. Proc Natl Acad Sci U S A. 2001;98:6453-8 pubmed
    ..We conclude that the beta2 subunit of the nicotinic acetylcholine receptor is necessary for the anatomical and functional development of the visual system. ..
  40. Pilz A, Le Tissier P, Moseley H, Peters J, Abbott C. Mapping of the structural gene for S-adenosyl homocysteine hydrolase to mouse chromosome 2, and related sequences to chromosomes 8 and X. Mamm Genome. 1992;3:633-6 pubmed
    ..One, Ahcy-rs1, was mapped to Chr 8 in the BXH recombinant inbred strains, and the other, Ahcy-rs2, shows a pattern of inheritance consistent with X-linkage. ..
  41. Krasteva G, Canning B, Hartmann P, Veres T, Papadakis T, Mühlfeld C, et al. Cholinergic chemosensory cells in the trachea regulate breathing. Proc Natl Acad Sci U S A. 2011;108:9478-83 pubmed publisher
    ..This identifies brush cells as cholinergic sensors of the chemical composition of the lower airway luminal microenvironment that are directly linked to the regulation of respiration...
  42. Drescher D, Khan K, Green G, Morley B, Beisel K, Kaul H, et al. Analysis of nicotinic acetylcholine receptor subunits in the cochlea of the mouse. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995;112:267-73 pubmed
    ..The presence of messages corresponding to the muscle-type beta 1 and neuronal-type nAChR subunits may be correlated with the atypical cholinergic response of cochlear hair cells to agonists and antagonists. ..
  43. Gahring L, Persiyanov K, Dunn D, Weiss R, Meyer E, Rogers S. Mouse strain-specific nicotinic acetylcholine receptor expression by inhibitory interneurons and astrocytes in the dorsal hippocampus. J Comp Neurol. 2004;468:334-46 pubmed
  44. Cheng S, Amici S, Ren X, McKay S, Treuil M, Lindstrom J, et al. Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta. J Biol Chem. 2009;284:23251-9 pubmed publisher
    ..Our results provide novel insights as to possible mechanisms by which dysfunctional neurexins, through downstream effects on alpha4beta2 AChRs, may contribute to the etiology of these neurological disorders. ..
  45. Avraam J, Cohen G, Drago J, Frappell P. Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia. Respir Physiol Neurobiol. 2015;208:29-36 pubmed publisher
    ..001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress. ..
  46. Cannata D, Finkelstein D, Gantois I, Teper Y, Drago J, West J. Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor. J Muscle Res Cell Motil. 2009;30:73-83 pubmed publisher
    We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4) encoding the alpha4 subunit of neuronal nicotinic acetylcholine receptor (nAChR)...
  47. McColl C, Horne M, Finkelstein D, Wong J, Berkovic S, Drago J. Electroencephalographic characterisation of pentylenetetrazole-induced seizures in mice lacking the alpha 4 subunit of the neuronal nicotinic receptor. Neuropharmacology. 2003;44:234-43 pubmed
    ..002) and continuous fast activity (P=0.017) compared to controls. These findings demonstrate that intact alpha 4 nAChR subunits provide significant in vivo protection against the proconvulsant effects of GABA antagonism. ..
  48. Didier M, Bix G, Berman S, Bursztajn S. Expression of the alpha 4 neuronal nicotinic acetylcholine receptor subunit in the developing mouse hippocampus. Int J Dev Neurosci. 1995;13:703-13 pubmed
    ..The transient profile of alpha 4 expression suggests that nAChRs may participate in the early postnatal maturation of hippocampal circuity. ..
  49. Lange Asschenfeldt C, Schäble S, Suvorava T, Fahimi E, Bisha M, Stermann T, et al. Effects of varenicline on alpha4-containing nicotinic acetylcholine receptor expression and cognitive performance in mice. Neuropharmacology. 2016;107:100-110 pubmed publisher
    ..In parallel, protein, but not mRNA expression was upregulated, suggesting a posttranscriptional mechanism. Our findings suggest a beneficial effect of varenicline on cognitive dysfunction. ..
  50. Chakrabarty K, von Oerthel L, Hellemons A, Clotman F, Espana A, Groot Koerkamp M, et al. Genome wide expression profiling of the mesodiencephalic region identifies novel factors involved in early and late dopaminergic development. Biol Open. 2012;1:693-704 pubmed publisher
    ..Furthermore, we provide evidence of two divergent regulatory pathways resulting in the expression of Chrna6 and Chrnb3 respectively. ..
  51. Tekinay A, Nong Y, Miwa J, Lieberam I, Ibanez Tallon I, Greengard P, et al. A role for LYNX2 in anxiety-related behavior. Proc Natl Acad Sci U S A. 2009;106:4477-82 pubmed publisher
  52. Karadsheh M, Shah M, Tang X, Macdonald R, Stitzel J. Functional characterization of mouse alpha4beta2 nicotinic acetylcholine receptors stably expressed in HEK293T cells. J Neurochem. 2004;91:1138-50 pubmed
    ..Consequently, at low nanomolar concentrations, MLA may not be as selective for alpha7-containing nAchRs as previously thought. ..
  53. Greenfield A, Dunn T, Muscat G, Koopman P. The Sry-related gene Sox18 maps to distal mouse chromosome 2. Genomics. 1996;36:558-9 pubmed
  54. Hu J, Zhu C, Liu Y, Wang F, Huang Z, Fan W, et al. Dynamic alterations of gene expression of nicotinic acetylcholine receptor ?7, ?4 and ?2 subunits in an acute MPTP-lesioned mouse model. Neurosci Lett. 2011;494:232-6 pubmed publisher
    ..These data suggest that therapeutic strategies targeted toward nAChR ?7, ?4 and ?2 subunits may have potential for developing new treatments for PD. ..
  55. Gahring L, Rogers S. Nicotinic acetylcholine receptor expression in the hippocampus of 27 mouse strains reveals novel inhibitory circuitry. Hippocampus. 2008;18:737-49 pubmed publisher
    ..These findings define a genetic frame-work in which the strain-specific responses to nicotine include underlying contributions by the varied anatomical context in which nAChRs are expressed. ..
  56. Marks M, Wageman C, Grady S, Gopalakrishnan M, Briggs C. Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain. Biochem Pharmacol. 2009;78:795-802 pubmed publisher
    ..As one form of alpha6beta2* nAChR is sensitive to sub-muM concentrations, we propose that this receptor in particular may contribute to the enhanced cognitive performance following low doses of ABT-089. ..
  57. Quik M, Campos C, Grady S. Multiple CNS nicotinic receptors mediate L-dopa-induced dyskinesias: studies with parkinsonian nicotinic receptor knockout mice. Biochem Pharmacol. 2013;86:1153-62 pubmed publisher
    ..Thus drugs targeting one or multiple nAChRs may be optimal for reducing L-dopa-induced dyskinesias in Parkinson's disease. ..
  58. Shih D, Heimesaat M, Kuwajima S, Stein R, Wright C, Stoffel M. Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. Proc Natl Acad Sci U S A. 2002;99:3818-23 pubmed
    ..These studies also established polygenic mouse models for investigating the mechanisms contributing to beta-cell dysfunction in diabetes. ..
  59. Vandesquille M, Baudonnat M, Decorte L, Louis C, Lestage P, Beracochea D. Working memory deficits and related disinhibition of the cAMP/PKA/CREB are alleviated by prefrontal ?4?2*-nAChRs stimulation in aged mice. Neurobiol Aging. 2013;34:1599-609 pubmed publisher
    ..Thus, by targeting the ?4?2*-nicotinic receptor of the PL, S 38232 alleviates PL CREB overphosphorylation and restores WM in aged mice, which opens new pharmacologic perspectives of therapeutic strategy. ..
  60. Foong J, Hirst C, Hao M, McKeown S, Boesmans W, Young H, et al. Changes in Nicotinic Neurotransmission during Enteric Nervous System Development. J Neurosci. 2015;35:7106-15 pubmed publisher
    ..This is the first study to investigate the development of cholinergic transmission in the ENS. ..
  61. Kuo Y, Lucero L, Michaels J, Deluca D, Lukas R. Differential expression of nicotinic acetylcholine receptor subunits in fetal and neonatal mouse thymus. J Neuroimmunol. 2002;130:140-54 pubmed
    ..These studies suggest important roles for nAChR in immune system development and function and in the neuroimmune network. ..
  62. Darsow T, Booker T, Piña Crespo J, Heinemann S. Exocytic trafficking is required for nicotine-induced up-regulation of alpha 4 beta 2 nicotinic acetylcholine receptors. J Biol Chem. 2005;280:18311-20 pubmed
    ..Therefore, nicotine appears to regulate surface receptor levels at a step prior to initial insertion in the plasma membrane rather than by altering their endocytic trafficking or degradation rates as had been previously suggested. ..
  63. Ishizuka T, Ozawa A, Goshima H, Watanabe Y. Involvement of nicotinic acetylcholine receptor in the proliferation of mouse induced pluripotent stem cells. Life Sci. 2012;90:637-48 pubmed publisher
    ..The present study indicates that stimulation of ?(4)-nAchR and ?(7)-nAchR may lead to a significant increase in the rate of mouse iPS cell proliferation through enhancement of the CaMK? signaling pathway. ..
  64. Stitzel J, Dobelis P, Jimenez M, Collins A. Long sleep and short sleep mice differ in nicotine-stimulated 86Rb+ efflux and alpha4 nicotinic receptor subunit cDNA sequence. Pharmacogenetics. 2001;11:331-9 pubmed
    ..we reported that a restriction fragment length polymorphism associated with the alpha4 nicotinic receptor gene (Chrna4) may play a role in regulating differential sensitivity of LS and SS mouse lines to the seizure-inducing effects ..
  65. Nichols W, Henderson B, Yu C, Parker R, RICHARDS C, Lester H, et al. Lynx1 shifts α4β2 nicotinic receptor subunit stoichiometry by affecting assembly in the endoplasmic reticulum. J Biol Chem. 2014;289:31423-32 pubmed publisher
    ..To our knowledge, these data represent the first test of the hypothesis that a lynx family member, or indeed any glycosylphosphatidylinositol-anchored protein, could act within the cell to alter assembly of a multisubunit protein. ..
  66. D Agostino M, Crespi A, Polishchuk E, Generoso S, Martire G, Colombo S, et al. ER reorganization is remarkably induced in COS-7 cells accumulating transmembrane protein receptors not competent for export from the endoplasmic reticulum. J Membr Biol. 2014;247:1149-59 pubmed publisher
    ..This finding suggests that COS-7 cells may be extremely useful to study the molecular mechanisms regulating endoplasmic reticulum size and architecture. ..
  67. Tapper A, McKinney S, Marks M, Lester H. Nicotine responses in hypersensitive and knockout alpha 4 mice account for tolerance to both hypothermia and locomotor suppression in wild-type mice. Physiol Genomics. 2007;31:422-8 pubmed
  68. Pilz A, Willer E, Povey S, Abbott C. The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) map to human chromosome 20, extending the known region of homology with mouse chromosome 2. Ann Hum Genet. 1992;56:289-93 pubmed
    ..1989; Bessis et al. 1990). We have utilized Southern blot analysis on human/rodent somatic cell hybrids to map the human homologues of both of these genes, PCK1 and CHRNA4, to human chromosome 20.
  69. Williamson C, Dutton E, Abbott C, Beechey C, Ball S, Peters J. Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed. Genet Res. 1995;65:83-93 pubmed
    ..E2f1 and Tcf4) that express transcription factors, 2 genes (Cyp24 and Pck1) that are involved in growth, 5 genes (Acra4, Edn3, Kcnb1, Mc3r and Ntsr) where a defect could lead to neurological and probably behavioural problems, and 3 ..
  70. Wieskopf J, Mathur J, Limapichat W, Post M, Al Qazzaz M, Sorge R, et al. The nicotinic ?6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors. Sci Transl Med. 2015;7:287ra72 pubmed publisher
    ..Finally, we establish the relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical and temporomandibular pain. ..
  71. McClure Begley T, King N, Collins A, Stitzel J, Wehner J, Butt C. Acetylcholine-stimulated [3H]GABA release from mouse brain synaptosomes is modulated by alpha4beta2 and alpha4alpha5beta2 nicotinic receptor subtypes. Mol Pharmacol. 2009;75:918-26 pubmed publisher
  72. Shih P, Engle S, Oh G, Deshpande P, Puskar N, Lester H, et al. Differential expression and function of nicotinic acetylcholine receptors in subdivisions of medial habenula. J Neurosci. 2014;34:9789-802 pubmed publisher
    ..Last, we characterized rostral and dorsomedial IPN neurons that receive input from MHbVL axons. Together, our data provide new details regarding neurophysiology and nAChR localization and function in cells within the MHbV. ..
  73. Jin X, Steinbach J. Potentiation of Neuronal Nicotinic Receptors by 17β-Estradiol: Roles of the Carboxy-Terminal and the Amino-Terminal Extracellular Domains. PLoS ONE. 2015;10:e0144631 pubmed publisher
    ..The role of the N-terminus appears to be independent of the C-terminal tryptophan and likely reflects an influence on conformational changes caused during channel activation by agonist and potentiation by estradiol. ..
  74. Kageyama Yahara N, Suehiro Y, Yamamoto T, Kadowaki M. IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors. Biochem Biophys Res Commun. 2008;377:321-5 pubmed publisher
    ..Our findings indicate that mucosal mast cell activation may be negatively regulated mainly through nAChR alpha7 subunit, suggesting that nAChRs are involved in neuronal-mucosal mast cell interactions. ..
  75. Skok M, Grailhe R, Changeux J. Nicotinic receptors regulate B lymphocyte activation and immune response. Eur J Pharmacol. 2005;517:246-51 pubmed
    ..This could contribute to immune depression found in tobacco smokers. ..
  76. Kutlu M, Holliday E, Gould T. High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction. Neurobiol Learn Mem. 2016;128:17-22 pubmed publisher
    ..These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction. ..
  77. Klaassen A, Glykys J, Maguire J, Labarca C, Mody I, Boulter J. Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy. Proc Natl Acad Sci U S A. 2006;103:19152-7 pubmed
    ..To examine possible mechanisms underlying this inherited epilepsy, we engineered two ADNFLE mutations (Chrna4(S252F) and Chrna4(+L264)) in mice...
  78. McClure Begley T, Esterlis I, Stone K, Lam T, Grady S, Colangelo C, et al. Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex. Eneuro. 2016;3: pubmed publisher
    ..The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets. ..
  79. Estakhr J, Abazari D, Frisby K, McIntosh J, Nashmi R. Differential Control of Dopaminergic Excitability and Locomotion by Cholinergic Inputs in Mouse Substantia Nigra. Curr Biol. 2017;27:1900-1914.e4 pubmed publisher
    ..Our findings provide novel insights on how cholinergic inputs to subregions of the SNc regulate the excitability of DA neurons differentially, resulting in different patterns of motor behavior. ..
  80. Fox A, Moonschi F, RICHARDS C. The nicotine metabolite, cotinine, alters the assembly and trafficking of a subset of nicotinic acetylcholine receptors. J Biol Chem. 2015;290:24403-12 pubmed publisher
    ..We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of α4β2 receptors to favor the high sensitivity (α4)2(β2)3 stoichiometry. ..
  81. Lykhmus O, Voytenko L, Koval L, Mykhalskiy S, Kholin V, Peschana K, et al. α7 Nicotinic acetylcholine receptor-specific antibody induces inflammation and amyloid β42 accumulation in the mouse brain to impair memory. PLoS ONE. 2015;10:e0122706 pubmed publisher
  82. Hoerder Suabedissen A, Oeschger F, Krishnan M, Belgard T, Wang W, Lee S, et al. Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia. Proc Natl Acad Sci U S A. 2013;110:3555-60 pubmed publisher
    ..Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders. ..