{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:00:04Z","timestamp":1790827204293,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T00:00:00Z","timestamp":1526428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Essential Tremor (ET) is one of the most common neurological diseases, with an estimated 7 million affected individuals in the US; the pathophysiology of the disorder is poorly understood. Recently, we identified a mutation (<jats:italic>KCNS2<\/jats:italic> (<jats:italic>Kv9.2<\/jats:italic>), c.1137\u2009T\u2009&gt;\u2009A, p.(D379E) in an electrically silent voltage-gated K<jats:sup>+<\/jats:sup> channel \u03b1-subunit, <jats:italic>Kv9.2<\/jats:italic>, in a family with ET, that modulates the activity of Kv2 channels. We have produced transgenic <jats:italic>Drosophila<\/jats:italic> lines that express either the human wild type Kv9.2 (hKv9.2) or the ET causing mutant Kv9.2 (hKv9.2-D379E) subunit in all neurons. We show that the hKv9.2 subunit modulates activity of endogenous <jats:italic>Drosophila<\/jats:italic> K<jats:sup>+<\/jats:sup> channel Shab. The mutant hKv9.2-D379E subunit showed significantly higher levels of Shab inactivation and a higher frequency of spontaneous firing rate consistent with neuronal hyperexcitibility. We also observed behavioral manifestations of nervous system dysfunction including effects on night time activity and sleep. This functional data further supports the pathogenicity of the <jats:italic>KCNS2<\/jats:italic> (p.D379E) mutation, consistent with our prior observations including co-segregation with ET in a family, a likely pathogenic change in the channel pore domain and absence from population databases. The <jats:italic>Drosophila<\/jats:italic> hKv9.2 transgenic model recapitulates several features of ET and may be employed to advance our understanding of ET disease pathogenesis.<\/jats:p>","DOI":"10.1038\/s41598-018-25949-w","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T11:25:45Z","timestamp":1525951545000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Drosophila Model of Essential Tremor"],"prefix":"10.1038","volume":"8","author":[{"given":"Philip","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Sonti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zagaa","family":"Odgerel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Santa-Maria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-0501","authenticated-orcid":false,"given":"Brian D.","family":"McCabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-7051","authenticated-orcid":false,"given":"Krasimira","family":"Tsaneva-Atanasova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elan D.","family":"Louis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J. L.","family":"Hodge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine N.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,16]]},"reference":[{"issue":"Suppl 1","key":"25949_CR1","doi-asserted-by":"publisher","first-page":"S88","DOI":"10.1016\/S1353-8020(13)70023-3","volume":"20","author":"ED Louis","year":"2014","unstructured":"Louis, E. D. Re-thinking the biology of essential tremor: from models to morphology. Parkinsonism Relat Disord 20(Suppl 1), S88\u201393, https:\/\/doi.org\/10.1016\/S1353-8020(13)70023-3 (2014).","journal-title":"Parkinsonism Relat Disord"},{"key":"25949_CR2","doi-asserted-by":"publisher","unstructured":"Liu, X. et al. Identification of candidate genes for familial early-onset essential tremor. European journal of human genetics: EJHG, https:\/\/doi.org\/10.1038\/ejhg.2015.228 (2015).","DOI":"10.1038\/ejhg.2015.228"},{"key":"25949_CR3","doi-asserted-by":"publisher","first-page":"24371","DOI":"10.1074\/jbc.272.39.24371","volume":"272","author":"M Salinas","year":"1997","unstructured":"Salinas, M., Duprat, F., Heurteaux, C., Hugnot, J. P. & Lazdunski, M. New modulatory alpha subunits for mammalian Shab K+ channels. J Biol Chem 272, 24371\u201324379 (1997).","journal-title":"J Biol Chem"},{"key":"25949_CR4","doi-asserted-by":"publisher","first-page":"6238","DOI":"10.1523\/JNEUROSCI.0862-06.2006","volume":"26","author":"A Ueda","year":"2006","unstructured":"Ueda, A. & Wu, C. F. Distinct frequency-dependent regulation of nerve terminal excitability and synaptic transmission by IA and IK potassium channels revealed by Drosophila Shaker and Shab mutations. J Neurosci 26, 6238\u20136248, https:\/\/doi.org\/10.1523\/JNEUROSCI.0862-06.2006 (2006).","journal-title":"J Neurosci"},{"key":"25949_CR5","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/0896-6273(91)90279-9","volume":"7","author":"M Covarrubias","year":"1991","unstructured":"Covarrubias, M., Wei, A. A. & Salkoff, L. Shaker, Shal, Shab, and Shaw express independent K+ current systems. Neuron 7, 763\u2013773 (1991).","journal-title":"Neuron"},{"key":"25949_CR6","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1523\/JNEUROSCI.15-03-01741.1995","volume":"15","author":"S Tsunoda","year":"1995","unstructured":"Tsunoda, S. & Salkoff, L. Genetic analysis of Drosophila neurons: Shal, Shaw, and Shab encode most embryonic potassium currents. J Neurosci 15, 1741\u20131754 (1995).","journal-title":"J Neurosci"},{"key":"25949_CR7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1089\/ars.2014.6007","volume":"22","author":"C Peers","year":"2015","unstructured":"Peers, C. & Boyle, J. P. Oxidative modulation of K+ channels in the central nervous system in neurodegenerative diseases and aging. Antioxid Redox Signal 22, 505\u2013521, https:\/\/doi.org\/10.1089\/ars.2014.6007 (2015).","journal-title":"Antioxid Redox Signal"},{"key":"25949_CR8","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1055\/s-2004-819461","volume":"35","author":"A Klein","year":"2004","unstructured":"Klein, A., Boltshauser, E., Jen, J. & Baloh, R. W. Episodic ataxia type 1 with distal weakness: a novel manifestation of a potassium channelopathy. Neuropediatrics 35, 147\u2013149, https:\/\/doi.org\/10.1055\/s-2004-817921 (2004).","journal-title":"Neuropediatrics"},{"key":"25949_CR9","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/ng1758","volume":"38","author":"MF Waters","year":"2006","unstructured":"Waters, M. F. et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nature genetics 38, 447\u2013451, https:\/\/doi.org\/10.1038\/ng1758 (2006).","journal-title":"Nature genetics"},{"key":"25949_CR10","doi-asserted-by":"publisher","first-page":"7677","DOI":"10.1523\/JNEUROSCI.23-20-07677.2003","volume":"23","author":"H Matsukawa","year":"2003","unstructured":"Matsukawa, H., Wolf, A. M., Matsushita, S., Joho, R. H. & Knopfel, T. Motor dysfunction and altered synaptic transmission at the parallel fiber-Purkinje cell synapse in mice lacking potassium channels Kv3.1 and Kv3.3. J Neurosci 23, 7677\u20137684 (2003).","journal-title":"J Neurosci"},{"key":"25949_CR11","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1111\/j.0953-816X.2004.03385.x","volume":"19","author":"A McMahon","year":"2004","unstructured":"McMahon, A. et al. Allele-dependent changes of olivocerebellar circuit properties in the absence of the voltage-gated potassium channels Kv3.1 and Kv3.3. Eur J Neurosci 19, 3317\u20133327, https:\/\/doi.org\/10.1111\/j.0953-816X.2004.03385.x (2004).","journal-title":"Eur J Neurosci"},{"key":"25949_CR12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1046\/j.1601-183x.2003.00054.x","volume":"3","author":"F Espinosa","year":"2004","unstructured":"Espinosa, F., Marks, G., Heintz, N. & Joho, R. H. Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels. Genes Brain Behav 3, 90\u2013100 (2004).","journal-title":"Genes Brain Behav"},{"key":"25949_CR13","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/bs.apcsb.2015.10.006","volume":"103","author":"P Kumar","year":"2016","unstructured":"Kumar, P., Kumar, D., Jha, S. K., Jha, N. K. & Ambasta, R. K. Ion Channels in Neurological Disorders. Adv Protein Chem Struct Biol 103, 97\u2013136, https:\/\/doi.org\/10.1016\/bs.apcsb.2015.10.006 (2016).","journal-title":"Adv Protein Chem Struct Biol"},{"key":"25949_CR14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1159\/000213307","volume":"38","author":"E Le Bourg","year":"1992","unstructured":"Le Bourg, E. & Lints, F. A. Hypergravity and aging in Drosophila melanogaster. 4. Climbing activity. Gerontology 38, 59\u201364 (1992).","journal-title":"Gerontology"},{"key":"25949_CR15","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1038\/nature03486","volume":"434","author":"C Cirelli","year":"2005","unstructured":"Cirelli, C. et al. Reduced sleep in Drosophila Shaker mutants. Nature 434, 1087\u20131092, https:\/\/doi.org\/10.1038\/nature03486 (2005).","journal-title":"Nature"},{"key":"25949_CR16","doi-asserted-by":"publisher","first-page":"5384","DOI":"10.1523\/JNEUROSCI.0108-07.2007","volume":"27","author":"D Bushey","year":"2007","unstructured":"Bushey, D., Huber, R., Tononi, G. & Cirelli, C. Drosophila Hyperkinetic mutants have reduced sleep and impaired memory. J Neurosci 27, 5384\u20135393, https:\/\/doi.org\/10.1523\/JNEUROSCI.0108-07.2007 (2007).","journal-title":"J Neurosci"},{"key":"25949_CR17","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1212\/01.wnl.0000279339.87987.d7","volume":"69","author":"ED Louis","year":"2007","unstructured":"Louis, E. D., Benito-Leon, J., Ottman, R. & Bermejo-Pareja, F. Neurological Disorders in Central Spain Study, G. A population-based study of mortality in essential tremor. Neurology 69, 1982\u20131989, https:\/\/doi.org\/10.1212\/01.wnl.0000279339.87987.d7 (2007).","journal-title":"Neurology"},{"key":"25949_CR18","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1098\/rstb.1999.0458","volume":"354","author":"NM Bonini","year":"1999","unstructured":"Bonini, N. M. A genetic model for human polyglutamine-repeat disease in Drosophila melanogaster. Philos Trans R Soc Lond B Biol Sci 354, 1057\u20131060, https:\/\/doi.org\/10.1098\/rstb.1999.0458 (1999).","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"25949_CR19","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/nature04788","volume":"441","author":"J Park","year":"2006","unstructured":"Park, J. et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441, 1157\u20131161, https:\/\/doi.org\/10.1038\/nature04788 (2006).","journal-title":"Nature"},{"key":"25949_CR20","doi-asserted-by":"publisher","first-page":"4078","DOI":"10.1073\/pnas.0737556100","volume":"100","author":"JC Greene","year":"2003","unstructured":"Greene, J. C. et al. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 100, 4078\u20134083, https:\/\/doi.org\/10.1073\/pnas.0737556100 (2003).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25949_CR21","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1534\/g3.113.006205","volume":"3","author":"TF Flood","year":"2013","unstructured":"Flood, T. F., Gorczyca, M., White, B. H., Ito, K. & Yoshihara, M. A large-scale behavioral screen to identify neurons controlling motor programs in the Drosophilabrain. G3 (Bethesda) 3, 1629\u20131637, https:\/\/doi.org\/10.1534\/g3.113.006205 (2013).","journal-title":"G3 (Bethesda)"},{"key":"25949_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/BF00195964","volume":"171","author":"JE Engel","year":"1992","unstructured":"Engel, J. E. & Wu, C. F. Interactions of membrane excitability mutations affecting potassium and sodium currents in the flight and giant fiber escape systems of Drosophila. J Comp Physiol A 171, 93\u2013104 (1992).","journal-title":"J Comp Physiol A"},{"key":"25949_CR23","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/genetics\/61.2.399","volume":"61","author":"WD Kaplan","year":"1969","unstructured":"Kaplan, W. D. & Trout, W. E. 3rd The behavior of four neurological mutants of Drosophila. Genetics 61, 399\u2013409 (1969).","journal-title":"Genetics"},{"key":"25949_CR24","doi-asserted-by":"publisher","first-page":"5958","DOI":"10.1523\/JNEUROSCI.20-16-05958.2000","volume":"20","author":"JW Wang","year":"2000","unstructured":"Wang, J. W., Humphreys, J. M., Phillips, J. P., Hilliker, A. J. & Wu, C. F. A novel leg-shaking Drosophila mutant defective in a voltage-gated K(+)current and hypersensitive to reactive oxygen species. J Neurosci 20, 5958\u20135964 (2000).","journal-title":"J Neurosci"},{"key":"25949_CR25","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/neu.20126","volume":"63","author":"JJ Hodge","year":"2005","unstructured":"Hodge, J. J., Choi, J. C., O\u2019Kane, C. J. & Griffith, L. C. Shaw potassium channel genes in. Drosophila. J Neurobiol 63, 235\u2013254, https:\/\/doi.org\/10.1002\/neu.20126 (2005).","journal-title":"Drosophila. J Neurobiol"},{"key":"25949_CR26","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1213\/00000539-199311000-00023","volume":"77","author":"RV Reddy","year":"1993","unstructured":"Reddy, R. V. et al. Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol. Anesth Analg 77, 1008\u20131011 (1993).","journal-title":"Anesth Analg"},{"key":"25949_CR27","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1001\/archneur.1997.00550150047015","volume":"54","author":"J Jankovic","year":"1997","unstructured":"Jankovic, J., Beach, J., Pandolfo, M. & Patel, P. I. Familial essential tremor in 4 kindreds. Prospects for genetic mapping. Arch Neurol 54, 289\u2013294 (1997).","journal-title":"Arch Neurol"},{"key":"25949_CR28","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1006\/exnr.1995.1050","volume":"134","author":"A Richter","year":"1995","unstructured":"Richter, A. et al. The \u201ccampus syndrome\u201d in pigs: neurological, neurophysiological, and neuropharmacological characterization of a new genetic animal model of high-frequency tremor. Exp Neurol 134, 205\u2013213, https:\/\/doi.org\/10.1006\/exnr.1995.1050 (1995).","journal-title":"Exp Neurol"},{"key":"25949_CR29","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/nature16148","volume":"527","author":"C Chen","year":"2015","unstructured":"Chen, C. et al. Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature. Nature 527, 516\u2013520, https:\/\/doi.org\/10.1038\/nature16148 (2015).","journal-title":"Nature"},{"key":"25949_CR30","doi-asserted-by":"publisher","first-page":"13486","DOI":"10.1073\/pnas.1606547113","volume":"113","author":"E Buhl","year":"2016","unstructured":"Buhl, E. et al. Quasimodo mediates daily and acute light effects on Drosophila clock neuron excitability. Proc Natl Acad Sci USA 113, 13486\u201313491, https:\/\/doi.org\/10.1073\/pnas.1606547113 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25949_CR31","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1002\/mds.25590","volume":"28","author":"J Benito-Leon","year":"2013","unstructured":"Benito-Leon, J., Louis, E. D. & Bermejo-Pareja, F. Short sleep duration heralds essential tremor: a prospective, population-based study. Mov Disord 28, 1700\u20131707, https:\/\/doi.org\/10.1002\/mds.25590 (2013).","journal-title":"Mov Disord"},{"key":"25949_CR32","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jns.2016.10.006","volume":"371","author":"B Rohl","year":"2016","unstructured":"Rohl, B. et al. Daytime sleepiness and nighttime sleep quality across the full spectrum of cognitive presentations in essential tremor. J Neurol Sci 371, 24\u201331, https:\/\/doi.org\/10.1016\/j.jns.2016.10.006 (2016).","journal-title":"J Neurol Sci"},{"key":"25949_CR33","doi-asserted-by":"publisher","first-page":"498","DOI":"10.7916\/D80S01VK","volume":"7","author":"A Lenka","year":"2017","unstructured":"Lenka, A., Benito-Leon, J. & Louis, E. D. Is there a Premotor Phase of Essential Tremor? Tremor Other Hyperkinet Mov (N Y) 7, 498, https:\/\/doi.org\/10.7916\/D80S01VK (2017).","journal-title":"Tremor Other Hyperkinet Mov (N Y)"},{"key":"25949_CR34","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1016\/j.cub.2008.08.033","volume":"18","author":"V Sheeba","year":"2008","unstructured":"Sheeba, V. et al. Large ventral lateral neurons modulate arousal and sleep in Drosophila. Curr Biol 18, 1537\u20131545, https:\/\/doi.org\/10.1016\/j.cub.2008.08.033 (2008).","journal-title":"Curr Biol"},{"key":"25949_CR35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.nbd.2017.04.014","volume":"104","author":"H Julienne","year":"2017","unstructured":"Julienne, H., Buhl, E., Leslie, D. S. & Hodge, J. J. L. Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson\u2019s disease phenotypes. Neurobiol Dis 104, 15\u201323, https:\/\/doi.org\/10.1016\/j.nbd.2017.04.014 (2017).","journal-title":"Neurobiol Dis"},{"key":"25949_CR36","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1523\/JNEUROSCI.3915-05.2006","volume":"26","author":"MN Nitabach","year":"2006","unstructured":"Nitabach, M. N. et al. Electrical hyperexcitation of lateral ventral pacemaker neurons desynchronizes downstream circadian oscillators in the fly circadian circuit and induces multiple behavioral periods. J Neurosci 26, 479\u2013489, https:\/\/doi.org\/10.1523\/JNEUROSCI.3915-05.2006 (2006).","journal-title":"J Neurosci"},{"key":"25949_CR37","doi-asserted-by":"publisher","unstructured":"Bergareche, A. et al. SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy. Human molecular genetics, https:\/\/doi.org\/10.1093\/hmg\/ddv410 (2015).","DOI":"10.1093\/hmg\/ddv410"},{"key":"25949_CR38","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/jhg.2017.21","volume":"62","author":"XR Leng","year":"2017","unstructured":"Leng, X. R., Qi, X. H., Zhou, Y. T. & Wang, Y. P. Gain-of-function mutation p.Arg225Cys in SCN11A causes familial episodic pain and contributes to essential tremor. J Hum Genet 62, 641\u2013646, https:\/\/doi.org\/10.1038\/jhg.2017.21 (2017).","journal-title":"J Hum Genet"},{"key":"25949_CR39","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1126\/science.3059497","volume":"242","author":"RR Llinas","year":"1988","unstructured":"Llinas, R. R. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242, 1654\u20131664 (1988).","journal-title":"Science"},{"key":"25949_CR40","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1152\/physrev.00018.2002","volume":"83","author":"E Perez-Reyes","year":"2003","unstructured":"Perez-Reyes, E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83, 117\u2013161, https:\/\/doi.org\/10.1152\/physrev.00018.2002 (2003).","journal-title":"Physiol Rev"},{"key":"25949_CR41","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1523\/JNEUROSCI.2411-06.2007","volume":"27","author":"J Sarnthein","year":"2007","unstructured":"Sarnthein, J. & Jeanmonod, D. High thalamocortical theta coherence in patients with Parkinson\u2019s disease. J Neurosci 27, 124\u2013131, https:\/\/doi.org\/10.1523\/JNEUROSCI.2411-06.2007 (2007).","journal-title":"J Neurosci"},{"key":"25949_CR42","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1007\/s12311-015-0740-2","volume":"15","author":"P Filip","year":"2016","unstructured":"Filip, P., Lungu, O. V., Manto, M. U. & Bares, M. Linking Essential Tremor to the Cerebellum: Physiological Evidence. Cerebellum 15, 774\u2013780, https:\/\/doi.org\/10.1007\/s12311-015-0740-2 (2016).","journal-title":"Cerebellum"},{"key":"25949_CR43","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/BF00585623","volume":"414","author":"CM Sinton","year":"1989","unstructured":"Sinton, C. M., Krosser, B. I., Walton, K. D. & Llinas, R. R. The effectiveness of different isomers of octanol as blockers of harmaline-induced tremor. Pflugers Arch 414, 31\u201336 (1989).","journal-title":"Pflugers Arch"},{"key":"25949_CR44","doi-asserted-by":"publisher","unstructured":"Handforth, A. Harmaline tremor: underlying mechanisms in a potential animal model of essential tremor. Tremor Other Hyperkinet Mov (N Y) 2, https:\/\/doi.org\/10.7916\/D8TD9W2P (2012).","DOI":"10.7916\/D8TD9W2P"},{"key":"25949_CR45","doi-asserted-by":"publisher","first-page":"e42102","DOI":"10.1371\/journal.pone.0042102","volume":"7","author":"JW Wang","year":"2012","unstructured":"Wang, J. W., Beck, E. S. & McCabe, B. D. A modular toolset for recombination transgenesis and neurogenetic analysis of Drosophila. PLoS One 7, e42102, https:\/\/doi.org\/10.1371\/journal.pone.0042102 (2012).","journal-title":"PLoS One"},{"key":"25949_CR46","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/BF00268810","volume":"152","author":"Y Nogi","year":"1977","unstructured":"Nogi, Y., Matsumoto, K., Toh-e, A. & Oshima, Y. Interaction of super-repressible and dominant constitutive mutations for the synthesis of galactose pathway enzymes in Saccharomyces cerevisiae. Mol Gen Genet 152, 137\u2013144 (1977).","journal-title":"Mol Gen Genet"},{"key":"25949_CR47","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/BF00332719","volume":"195","author":"Y Nogi","year":"1984","unstructured":"Nogi, Y., Shimada, H., Matsuzaki, Y., Hashimoto, H. & Fukasawa, T. Regulation of expression of the galactose gene cluster in Saccharomyces cerevisiae. II. The isolation and dosage effect of the regulatory gene GAL80. Mol Gen Genet 195, 29\u201334 (1984).","journal-title":"Mol Gen Genet"},{"key":"25949_CR48","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1128\/MCB.7.10.3446","volume":"7","author":"NF Lue","year":"1987","unstructured":"Lue, N. F., Chasman, D. I., Buchman, A. R. & Kornberg, R. D. Interaction of GAL4 and GAL80 gene regulatory proteins in vitro. Mol Cell Biol 7, 3446\u20133451 (1987).","journal-title":"Mol Cell Biol"},{"key":"25949_CR49","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0531-5565(78)90012-8","volume":"13","author":"B Ganetzky","year":"1978","unstructured":"Ganetzky, B. & Flanagan, J. R. On the relationship between senescence and age-related changes in two wild-type strains of Drosophila melanogaster. Exp Gerontol 13, 189\u2013196 (1978).","journal-title":"Exp Gerontol"},{"key":"25949_CR50","doi-asserted-by":"publisher","DOI":"10.3791\/50068","author":"NJ Linford","year":"2013","unstructured":"Linford, N. J., Bilgir, C., Ro, J. & Pletcher, S. D. Measurement of lifespan in Drosophila melanogaster. J Vis Exp. https:\/\/doi.org\/10.3791\/50068 (2013).","journal-title":"J Vis Exp"},{"key":"25949_CR51","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.2337\/diabetes.55.04.06.db05-0788","volume":"55","author":"J Herrington","year":"2006","unstructured":"Herrington, J. et al. Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion. Diabetes 55, 1034\u20131042 (2006).","journal-title":"Diabetes"},{"key":"25949_CR52","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/bs.mie.2014.10.017","volume":"552","author":"M Schlichting","year":"2015","unstructured":"Schlichting, M. & Helfrich-Forster, C. Photic entrainment in Drosophila assessed by locomotor activity recordings. Methods Enzymol 552, 105\u2013123, https:\/\/doi.org\/10.1016\/bs.mie.2014.10.017 (2015).","journal-title":"Methods Enzymol"},{"key":"25949_CR53","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1113\/jphysiol.1952.sp004764","volume":"117","author":"AL Hodgkin","year":"1952","unstructured":"Hodgkin, A. L. & Huxley, A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117, 500\u2013544 (1952).","journal-title":"J Physiol"},{"key":"25949_CR54","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1126\/science.1169657","volume":"326","author":"MD Belle","year":"2009","unstructured":"Belle, M. D., Diekman, C. O., Forger, D. B. & Piggins, H. D. Daily electrical silencing in the mammalian circadian clock. Science 326, 281\u2013284, https:\/\/doi.org\/10.1126\/science.1169657 (2009).","journal-title":"Science"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25949-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25949-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25949-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T05:23:50Z","timestamp":1671600230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25949-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,16]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["25949"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-25949-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,16]]},"assertion":[{"value":"27 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7664"}}