generalized tonic–clonic seizures; idiopathic generalized epilepsy; spike and wave discharges; thalamocortical network; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all)
Abstract :
[en] The use of animal models of idiopathic generalized epilepsy (IGE) is of great importance in the field of epilepsy research, with IGE affecting more than 20 million people worldwide. IGEs are characterized by a high degree of genetic heterogeneity, which makes it difficult to understand the underlying mechanisms leading to seizures. The development of animal models, whether spontaneous or resulting from genetic manipulation, has significantly contributed to our understanding of the pathological processes underlying certain IGEs, notably absence epilepsy. Research suggests that the concept of generalized epilepsy covering the whole brain should be replaced by a model in which the thalamus and its various nuclei are integrated into thalamo-cortical loops. These then assume distinct roles in the generation and generalization of seizures, which may differ across the spectrum of IGE disorders. The study of epileptogenesis is also essential: this area of research, grounded in systematic developmental neuroscience, examines the intermediate stages of neuronal activity to determine when, and how, functional development diverges between healthy and pathological states. Understanding nervous system development requires a comprehensive view of how anatomic, molecular, and genetics factors relate to neuronal activity. The emerging use of optogenetic methods and human assembloids will greatly aid our understanding of the mechanisms underlying these processes.
Lakaye, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; WELBIO Department, WEL Research Institute, Avenue Pasteur 6, 1300 Wavre, Belgium
Language :
English
Title :
Genetic Animal Models of Idiopathic Generalized Epilepsies: What Can We Learn from Them?
Publication date :
26 May 2025
Journal title :
Biomedicines
eISSN :
2227-9059
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
ULiège - Université de Liège F.R.S.-FNRS - Fonds de la Recherche Scientifique WRI. WELBIO - Wel Research Institute. Walloon Excellence in Life Sciences and Biotechnology Fonds Léon Fredericq Fondation Pierre et Simone Clerdent FMRE - Fondation Médicale Reine Elisabeth
Funding text :
The work performed in the laboratory is supported by ULi\u00E8ge (Cr\u00E9dit Classique), the F.R.S.-FNRS (PDR T.0185.20; EOS 0019118F-RG36), the WEL Research Institute (CR-2022A-12), the Fonds Leon Fredericq, the Foundation Simone et Pierre Clerdent, the Fondation M\u00E9dicale Reine Elisabeth, the ERANET Neuron (STEM-MCD and NeuroTalk), the Win2Wal (ChipOmics; #2010126), and the ERC-Synergy (UNFOLD).
Wirrell E.C. Nabbout R. Scheffer I.E. Alsaadi T. Bogacz A. French J.A. Hirsch E. Jain S. Kaneko S. Riney K. et al. Methodology for Classification and Definition of Epilepsy Syndromes with List of Syndromes: Report of the ILAE Task Force on Nosology and Definitions Epilepsia 2022 63 1333 1348 10.1111/epi.17237 35503715
Hirsch E. French J. Scheffer I.E. Bogacz A. Alsaadi T. Sperling M.R. Abdulla F. Zuberi S.M. Trinka E. Specchio N. et al. ILAE Definition of the Idiopathic Generalized Epilepsy Syndromes: Position Statement by the ILAE Task Force on Nosology and Definitions Epilepsia 2022 63 1475 1499 10.1111/epi.17236 35503716
Lennox W.G. The Heredity of Epilepsy as Told by Relatives and Twins J. Am. Med. Assoc. 1951 146 529 536 10.1001/jama.1951.03670060005002 14832012
Qureshi I.A. Mehler M.F. Epigenetic Mechanisms Underlying Human Epileptic Disorders and the Process of Epileptogenesis Neurobiol. Dis. 2010 39 53 60 10.1016/j.nbd.2010.02.005
Wang G.D. Dai Z.Y. Song W.G. Wang S.F. Shi H.C. Pan P.L. Chen F. Xu Y. Zhong J.G. Grey Matter Anomalies in Drug-Naïve Childhood Absence Epilepsy: A Voxel-Based Morphometry Study with MRI at 3.0T Epilepsy Res. 2016 124 63 66 10.1016/j.eplepsyres.2016.05.003
Caplan R. Levitt J. Siddarth P. Wu K.N. Gurbani S. Sankar R. Shields W.D. Frontal and Temporal Volumes in Childhood Absence Epilepsy Epilepsia 2009 50 2466 2472 10.1111/j.1528-1167.2009.02198.x
Chan C.H. Briellmann R.S. Pell G.S. Scheffer I.E. Abbott D.F. Jackson G.D. Thalamic Atrophy in Childhood Absence Epilepsy Epilepsia 2006 47 399 405 10.1111/j.1528-1167.2006.00435.x
Tosun D. Siddarth P. Toga A.W. Hermann B. Caplan R. Effects of Childhood Absence Epilepsy on Associations between Regional Cortical Morphometry and Aging and Cognitive Abilities Hum. Brain Mapp. 2011 32 580 591 10.1002/hbm.21045
Corrêa D.G. Ventura N. Zimmermann N. Doring T.M. Tukamoto G. Leme J. Pereira M. D’Andrea I. Rêgo C. Alves-Leon S.V. et al. Evaluation of Deep Gray Matter Volume, Cortical Thickness and White Matter Integrity in Patients with Typical Absence Epilepsy: A Study Using Voxelwise-Based Techniques Neuroradiology 2017 59 237 245 10.1007/s00234-017-1782-6
Verrotti A. Matricardi S. Rinaldi V.E. Prezioso G. Coppola G. Neuropsychological Impairment in Childhood Absence Epilepsy: Review of the Literature J. Neurol. Sci. 2015 359 59 66 10.1016/j.jns.2015.10.035
Hirose S. Mutant GABA(A) Receptor Subunits in Genetic (Idiopathic) Epilepsy Prog. Brain Res. 2014 213 55 85 10.1016/B978-0-444-63326-2.00003-X 25194483
Singh B. Monteil A. Bidaud I. Sugimoto Y. Suzuki T. Hamano S.I. Oguni H. Osawa M. Alonso M.E. Delgado-Escueta A.V. et al. Mutational Analysis of CACNA1G in Idiopathic Generalized Epilepsy. Mutation in Brief #962. Online Hum. Mutat. 2007 28 524 525 10.1002/HUMU.9491
Wang J. Zhang Y. Liang J. Pan H. Wu H. Xu K. Liu X. Jiang Y. Shen Y. Wu X. CACNA1I Is Not Associated with Childhood Absence Epilepsy in the Chinese Han Population Pediatr. Neurol. 2006 35 187 190 10.1016/j.pediatrneurol.2006.03.006 16939858
Peloquin J.B. Khosravani H. Barr W. Bladen C. Evans R. Mezeyova J. Parker D. Snutch T.P. McRory J.E. Zamponi G.W. Functional Analysis of Ca3.2 T-Type Calcium Channel Mutations Linked to Childhood Absence Epilepsy Epilepsia 2006 47 655 658 10.1111/j.1528-1167.2006.00482.x
Marini C. Porro A. Rastetter A. Dalle C. Rivolta I. Bauer D. Oegema R. Nava C. Parrini E. Mei D. et al. HCN1 Mutation Spectrum: From Neonatal Epileptic Encephalopathy to Benign Generalized Epilepsy and Beyond Brain 2018 141 3160 3178 10.1093/brain/awy263 30351409
Abou-Khalil B. Auce P. Avbersek A. Bahlo M. Balding D.J. Bast T. Baum L. Becker A.J. Becker F. Berghuis B. et al. Genome-Wide Mega-Analysis Identifies 16 Loci and Highlights Diverse Biological Mechanisms in the Common Epilepsies Nat. Commun. 2018 9 5269 10.1038/S41467-018-07524-Z
Stevelink R. Campbell C. Chen S. Abou-Khalil B. Adesoji O.M. Afawi Z. Amadori E. Anderson A. Anderson J. Andrade D.M. et al. GWAS Meta-Analysis of over 29,000 People with Epilepsy Identifies 26 Risk Loci and Subtype-Specific Genetic Architecture Nat. Genet. 2023 55 1471 1482 10.1038/S41588-023-01485-W
Avoli M. A Brief History on the Oscillating Roles of Thalamus and Cortex in Absence Seizures Epilepsia 2012 53 779 789 10.1111/j.1528-1167.2012.03421.x
Huguenard J. Current Controversy: Spikes, Bursts, and Synchrony in Generalized Absence Epilepsy: Unresolved Questions Regarding Thalamocortical Synchrony in Absence Epilepsy Epilepsy Curr. 2019 19 105 111 10.1177/1535759719835355
Wakamori M. Yamazaki K. Matsunodaira H. Teramoto T. Tanaka I. Niidome T. Sawada K. Nishizawa Y. Sekiguchi N. Mori E. et al. Single Tottering Mutations Responsible for the Neuropathic Phenotype of the P-Type Calcium Channel J. Biol. Chem. 1998 273 34857 34867 10.1074/jbc.273.52.34857
Isaacs K.R. Abbott L.C. Development of the Paramedian Lobule of the Cerebellum in Wild-Type and Tottering Mice Dev. Neurosci. 1992 14 386 393 10.1159/000111687
Levitt P. Noebels J.L. Mutant Mouse Tottering: Selective Increase of Locus Ceruleus Axons in a Defined Single-Locus Mutation Proc. Natl. Acad. Sci. USA 1981 78 4630 4634 10.1073/pnas.78.7.4630 6945603
Letts V.A. Felix R. Biddlecome G.H. Arikkath J. Mahaffey C.L. Valenzuela A. Bartlett F.S. Mori Y. Campbell K.P. Frankel W.N. The Mouse Stargazer Gene Encodes a Neuronal Ca2+-Channel Gamma Subunit Nat. Genet. 1998 19 340 347 10.1038/1228
Menuz K. Nicoll R.A. Loss of Inhibitory Neuron AMPA Receptors Contributes to Ataxia and Epilepsy in Stargazer Mice J. Neurosci. 2008 28 10599 10603 10.1523/JNEUROSCI.2732-08.2008 18923036
Leitch B. The Impact of Glutamatergic Synapse Dysfunction in the Corticothalamocortical Network on Absence Seizure Generation Front. Mol. Neurosci. 2022 15 836255 10.3389/fnmol.2022.836255
Adotevi N.K. Leitch B. Cortical Expression of AMPA Receptors during Postnatal Development in a Genetic Model of Absence Epilepsy Int. J. Dev. Neurosci. 2019 73 19 25 10.1016/j.ijdevneu.2018.12.006
Khan Z. Carey J. Park H.J. Lehar M. Lasker D. Jinnah H.A. Abnormal Motor Behavior and Vestibular Dysfunction in the Stargazer Mouse Mutant Neuroscience 2004 127 785 796 10.1016/j.neuroscience.2004.05.052 15283975
Burgess D.L. Jones J.M. Meisler M.H. Noebels J.L. Mutation of the Ca2+ Channel Beta Subunit Gene Cchb4 Is Associated with Ataxia and Seizures in the Lethargic (Lh) Mouse Cell 1997 88 385 392 10.1016/S0092-8674(00)81877-2
McEnery M.W. Copeland T.D. Vance C.L. Altered Expression and Assembly of N-Type Calcium Channel Alpha1B and Beta Subunits in Epileptic Lethargic (Lh/Lh) Mouse J. Biol. Chem. 1998 273 21435 21438 10.1074/jbc.273.34.21435
Lin F.H. Cao Z. Hosford D.A. Increased Number of GABAB Receptors in the Lethargic (Lh/Lh) Mouse Model of Absence Epilepsy Brain Res. 1993 608 101 106 10.1016/0006-8993(93)90779-M
Cox G.A. Lutz C.M. Yang C.L. Biemesderfer D. Bronson R.T. Fu A. Aronson P.S. Noebels J.L. Frankel W.N. Sodium/Hydrogen Exchanger Gene Defect in Slow-Wave Epilepsy Mutant Mice Cell 1997 91 139 148 10.1016/S0092-8674(01)80016-7 9335342
Vergnes M. Marescaux C. Micheletti G. Reis J. Depaulis A. Rumbach L. Warter J.M. Spontaneous Paroxysmal Electroclinical Patterns in Rat: A Model of Generalized Non-Convulsive Epilepsy Neurosci. Lett. 1982 33 97 101 10.1016/0304-3940(82)90136-7 6818498
Vergnes M. Marescaux C. Boehrer A. Depaulis A. Are Rats with Genetic Absence Epilepsy Behaviorally Impaired? Epilepsy Res. 1991 9 97 104 10.1016/0920-1211(91)90019-C
Jarre G. Altwegg-Boussac T. Williams M.S. Studer F. Chipaux M. David O. Charpier S. Depaulis A. Mahon S. Guillemain I. Building Up Absence Seizures in the Somatosensory Cortex: From Network to Cellular Epileptogenic Processes Cereb. Cortex 2017 27 4607 4623 10.1093/cercor/bhx174
Chahboune H. Mishra A.M. DeSalvo M.N. Staib L.H. Purcaro M. Scheinost D. Papademetris X. Fyson S.J. Lorincz M.L. Crunelli V. et al. DTI Abnormalities in Anterior Corpus Callosum of Rats with Spike-Wave Epilepsy Neuroimage 2009 47 459 466 10.1016/j.neuroimage.2009.04.060
Bouilleret V. Hogan R.E. Velakoulis D. Salzberg M.R. Wang L. Egan G.F. O’Brien T.J. Jones N.C. Morphometric Abnormalities and Hyperanxiety in Genetically Epileptic Rats: A Model of Psychiatric Comorbidity? Neuroimage 2009 45 267 274 10.1016/j.neuroimage.2008.12.019 19167503
McCafferty C. Gruenbaum B.F. Tung R. Li J.J. Zheng X. Salvino P. Vincent P. Kratochvil Z. Ryu J.H. Khalaf A. et al. Decreased but Diverse Activity of Cortical and Thalamic Neurons in Consciousness-Impairing Rodent Absence Seizures Nat. Commun. 2023 14 117 10.1038/s41467-022-35535-4
Rudolf G. Bihoreau M.T. Godfrey R.F. Wilder S.P. Cox R.D. Lathrop M. Marescaux C. Gauguier D. Polygenic Control of Idiopathic Generalized Epilepsy Phenotypes in the Genetic Absence Rats from Strasbourg (GAERS) Epilepsia 2004 45 301 308 10.1111/j.0013-9580.2004.50303.x
Holter J. Carter D. Leresche N. Crunelli V. Vincent P. A TASK3 Channel (KCNK9) Mutation in a Genetic Model of Absence Epilepsy J. Mol. Neurosci. 2005 25 37 51 10.1385/JMN:25:1:037
Powell K.L. Cain S.M. Ng C. Sirdesai S. David L.S. Kyi M. Garcia E. Tyson J.R. Reid C.A. Bahlo M. et al. A Cav3.2 T-Type Calcium Channel Point Mutation Has Splice-Variant-Specific Effects on Function and Segregates with Seizure Expression in a Polygenic Rat Model of Absence Epilepsy J. Neurosci. 2009 29 371 380 10.1523/JNEUROSCI.5295-08.2009
Casillas-Espinosa P.M. Lin R. Li R. Nandakumar N.M. Dawson G. Braine E.L. Martin B. Powell K.L. O’Brien T.J. Effects of the T-Type Calcium Channel CaV3.2 R1584P Mutation on Absence Seizure Susceptibility in GAERS and NEC Congenic Rats Models Neurobiol. Dis. 2023 184 106217 10.1016/j.nbd.2023.106217 37391087
Casillas-Espinosa P.M. Powell K.L. Zhu M. Campbell C.R. Maia J.M. Ren Z. Jones N.C. O’Brien T.J. Petrovski S. Evaluating Whole Genome Sequence Data from the Genetic Absence Epilepsy Rat from Strasbourg and Its Related Non-Epileptic Strain PLoS ONE 2017 12 0179924 10.1371/journal.pone.0179924 28708842
Tsakiridou E. Bertollini L. De Curtis M. Avanzini G. Pape H.C. Selective Increase in T-Type Calcium Conductance of Reticular Thalamic Neurons in a Rat Model of Absence Epilepsy J. Neurosci. 1995 15 3110 3117 10.1523/JNEUROSCI.15-04-03110.1995
Bessaïh T. Bourgeais L. Badiu C.I. Carter D.A. Toth T.I. Ruano D. Lambolez B. Crunelli V. Leresche N. Nucleus-Specific Abnormalities of GABAergic Synaptic Transmission in a Genetic Model of Absence Seizures J. Neurophysiol. 2006 96 3074 3081 10.1152/jn.00682.2006 16971676
Kuisle M. Wanaverbecg N. Brewster A.L. Frère S.G.A. Pinault D. Baram T.Z. Lüthi A. Functional Stabilization of Weakened Thalamic Pacemaker Channel Regulation in Rat Absence Epilepsy J. Physiol. 2006 575 83 100 10.1113/jphysiol.2006.110486
Kennard J.T.T. Barmanray R. Sampurno S. Ozturk E. Reid C.A. Paradiso L. D’Abaco G.M. Kaye A.H. Foote S.J. O’Brien T.J. et al. Stargazin and AMPA Receptor Membrane Expression Is Increased in the Somatosensory Cortex of Genetic Absence Epilepsy Rats from Strasbourg Neurobiol. Dis. 2011 42 48 54 10.1016/j.nbd.2011.01.003
Spreafico R. Mennini T. Danober L. Cagnotto A. Regondi M.C. Miari A. De Blas A. Vergnes M. Avanzini G. GABAA Receptor Impairment in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS): An Immunocytochemical and Receptor Binding Autoradiographic Study Epilepsy Res. 1993 15 229 238 10.1016/0920-1211(93)90060-K
Snead O.C. Depaulis A. Banerjee P.K. Hechler V. Vergnes M. The GABAA Receptor Complex in Experimental Absence Seizures in Rat: An Autoradiographic Study Neurosci. Lett. 1992 140 9 12 10.1016/0304-3940(92)90669-X
Sabers A. Møller A. Scheel-Krüger J. Mouritzen Dam A. No Loss in Total Neuron Number in the Thalamic Reticular Nucleus and Neocortex in the Genetic Absence Epilepsy Rats from Strasbourg Epilepsy Res. 1996 26 45 48 10.1016/S0920-1211(96)00038-1
Papp P. Kovács Z. Szocsics P. Juhász G. Maglóczky Z. Alterations in Hippocampal and Cortical Densities of Functionally Different Interneurons in Rat Models of Absence Epilepsy Epilepsy Res. 2018 145 40 50 10.1016/j.eplepsyres.2018.05.013
Dutuit M. Didier-Bazès M. Vergnes M. Mutin M. Conjard A. Akaoka H. Belin M.F. Touret M. Specific Alteration in the Expression of Glial Fibrillary Acidic Protein, Glutamate Dehydrogenase, and Glutamine Synthetase in Rats with Genetic Absence Epilepsy Glia 2000 32 15 24 10.1002/1098-1136(200010)32:1<15::AID-GLIA20>3.0.CO;2-# 10975907
Çavdar S. Kuvvet Y. Sur-Erdem I. Özgür M. Onat F. Relationships between Astrocytes and Absence Epilepsy in Rat: An Experimental Study Neurosci. Lett. 2019 712 134518 10.1016/j.neulet.2019.134518 31560994
Akin D. Ravizza T. Maroso M. Carcak N. Eryigit T. Vanzulli I. Aker R.G. Vezzani A. Onat F.Y. IL-1β Is Induced in Reactive Astrocytes in the Somatosensory Cortex of Rats with Genetic Absence Epilepsy at the Onset of Spike-and-Wave Discharges, and Contributes to Their Occurrence Neurobiol. Dis. 2011 44 259 269 10.1016/j.nbd.2011.05.015
Dutuit M. Touret M. Szymocha R. Nehlig A. Belin M.F. Didier-Bazès M. Decreased Expression of Glutamate Transporters in Genetic Absence Epilepsy Rats before Seizure Occurrence J. Neurochem. 2002 80 1029 1038 10.1046/j.0022-3042.2002.00768.x
Pirttimaki T. Parri H.R. Crunelli V. Astrocytic GABA Transporter GAT-1 Dysfunction in Experimental Absence Seizures J. Physiol. 2013 591 823 833 10.1113/jphysiol.2012.242016 23090943
Deransart C. Hellwig B. Heupel-Reuter M. Léger J.F. Heck D. Lücking C.H. Single-Unit Analysis of Substantia Nigra Pars Reticulata Neurons in Freely Behaving Rats with Genetic Absence Epilepsy Epilepsia 2003 44 1513 1520 10.1111/j.0013-9580.2003.26603.x
Deransart C. Riban V. Lê B.T. Marescaux C. Depaulis A. Dopamine in the Striatum Modulates Seizures in a Genetic Model of Absence Epilepsy in the Rat Neuroscience 2000 100 335 344 10.1016/S0306-4522(00)00266-9
De Borman B. Lakaye B. Minet A. Zorzi W. Vergnes M. Marescaux C. Grisar T. Expression of MRNA Encoding Alpha1E and Alpha1G Subunit in the Brain of a Rat Model of Absence Epilepsy Neuroreport 1999 10 569 574 10.1097/00001756-199902250-00023
van Luijtelaar G. Sitnikova E. Global and Focal Aspects of Absence Epilepsy: The Contribution of Genetic Models Neurosci. Biobehav. Rev. 2006 30 983 1003 10.1016/j.neubiorev.2006.03.002
van Luijtelaar E.L.J.M. Coenen A.M.L. Two Types of Electrocortical Paroxysms in an Inbred Strain of Rats Neurosci. Lett. 1986 70 393 397 10.1016/0304-3940(86)90586-0
Akman O. Demiralp T. Ates N. Onat F.Y. Electroencephalographic Differences between WAG/Rij and GAERS Rat Models of Absence Epilepsy Epilepsy Res. 2010 89 185 193 10.1016/j.eplepsyres.2009.12.005 20092980
Coenen A.M.L. Van Luijtelaar E.L.J.M. Genetic Animal Models for Absence Epilepsy: A Review of the WAG/Rij Strain of Rats Behav. Genet. 2003 33 635 655 10.1023/A:1026179013847 14574120
Mishra A.M. Bai X. Motelow J.E. Desalvo M.N. Danielson N. Sanganahalli B.G. Hyder F. Blumenfeld H. Increased Resting Functional Connectivity in Spike-Wave Epilepsy in WAG/Rij Rats Epilepsia 2013 54 1214 1222 10.1111/epi.12227 23815571
Gauguier D. Van Luijtelaar G. Thérèse Bihoreau M. Wilder S.P. Godfrey R.F. Vossen J. Coenen A. Cox R.D. Chromosomal Mapping of Genetic Loci Controlling Absence Epilepsy Phenotypes in the WAG/Rij Rat Epilepsia 2004 45 908 915 10.1111/j.0013-9580.2004.13104.x
Strauss U. Kole M.H.P. Bräuer A.U. Pahnke J. Bajorat R. Rolfs A. Nitsch R. Deisz R.A. An Impaired Neocortical Ih Is Associated with Enhanced Excitability and Absence Epilepsy Eur. J. Neurosci. 2004 19 3048 3058 10.1111/j.0953-816X.2004.03392.x
Kole M.H.P. Bräuer A.U. Stuart G.J. Inherited Cortical HCN1 Channel Loss Amplifies Dendritic Calcium Electrogenesis and Burst Firing in a Rat Absence Epilepsy Model J. Physiol. 2007 578 507 525 10.1113/jphysiol.2006.122028
Wemhöner K. Kanyshkova T. Silbernagel N. Fernandez-Orth J. Bittner S. Kiper A.K. Rinné S. Netter M.F. Meuth S.G. Budde T. et al. An N-Terminal Deletion Variant of HCN1 in the Epileptic WAG/Rij Strain Modulates HCN Current Densities Front. Mol. Neurosci. 2015 8 63 10.3389/fnmol.2015.00063
Broicher T. Kanyshkova T. Meuth P. Pape H.C. Budde T. Correlation of T-Channel Coding Gene Expression, IT, and the Low Threshold Ca2+ Spike in the Thalamus of a Rat Model of Absence Epilepsy Mol. Cell Neurosci. 2008 39 384 399 10.1016/j.mcn.2008.07.012
van de Bovenkamp-Janssen M.C. van der Kloet J.C. van Luijtelaar G. Roubos E.W. NMDA-NR1 and AMPA-GluR4 Receptor Subunit Immunoreactivities in the Absence Epileptic WAG/Rij Rat Epilepsy Res. 2006 69 119 128 10.1016/j.eplepsyres.2006.01.003
Ngomba R.T. Ferraguti F. Badura A. Citraro R. Santolini I. Battaglia G. Bruno V. De Sarro G. Simonyi A. van Luijtelaar G. et al. Positive Allosteric Modulation of Metabotropic Glutamate 4 (MGlu4) Receptors Enhances Spontaneous and Evoked Absence Seizures Neuropharmacology 2008 54 344 354 10.1016/j.neuropharm.2007.10.004
Flor P.J. Battaglia G. Nicoletti F. Gasparini F. Bruno V. Neuroprotective Activity of Metabotropic Glutamate Receptor Ligands Adv. Exp. Med. Biol. 2002 513 197 223 10.1007/978-1-4615-0123-7_7 12575822
Pisu M.G. Mostallino M.C. Dore R. Mura M.L. Maciocco E. Russo E. De Sarro G. Serra M. Neuroactive Steroids and GABAA Receptor Plasticity in the Brain of the WAG/Rij Rat, a Model of Absence Epilepsy J. Neurochem. 2008 106 2502 2514 10.1111/j.1471-4159.2008.05538.x 18624910
Merlo D. Mollinari C. Inaba Y. Cardinale A. Rinaldi A.M. D’Antuono M. D’Arcangelo G. Tancredi V. Ragsdale D. Avoli M. Reduced GABAB Receptor Subunit Expression and Paired-Pulse Depression in a Genetic Model of Absence Seizures Neurobiol. Dis. 2007 25 631 641 10.1016/j.nbd.2006.11.005
Karpova A.V. Bikbaev A.F. Coenen A.M.L. Van Luijtelaar G. Morphometric Golgi Study of Cortical Locations in WAG/Rij Rats: The Cortical Focus Theory Neurosci. Res. 2005 51 119 128 10.1016/j.neures.2004.10.004
Sitnikova E. Kulikova S. Birioukova L. Raevsky V.V. Cellular Neuropathology of Absence Epilepsy in the Neocortex: A Population of Glial Cells Rather than Neurons Is Impaired in Genetic Rat Model Acta Neurobiol. Exp. 2011 71 263 268 10.55782/ane-2011-1846 21731079
Knowles J.K. Xu H. Soane C. Batra A. Saucedo T. Frost E. Tam L.T. Fraga D. Ni L. Villar K. et al. Maladaptive Myelination Promotes Generalized Epilepsy Progression Nat. Neurosci. 2022 25 596 606 10.1038/s41593-022-01052-2
Schofield C.M. Kleiman-Weiner M. Rudolph U. Huguenard J.R. A Gain in GABAA Receptor Synaptic Strength in Thalamus Reduces Oscillatory Activity and Absence Seizures Proc. Natl. Acad. Sci. USA 2009 106 7630 7635 10.1073/pnas.0811326106
DeLorey T.M. Handforth A. Anagnostaras S.G. Homanics G.E. Minassian B.A. Asatourian A. Fanselow M.S. Delgado-Escueta A. Ellison G.D. Olsen R.W. Mice Lacking the Beta3 Subunit of the GABAA Receptor Have the Epilepsy Phenotype and Many of the Behavioral Characteristics of Angelman Syndrome J. Neurosci. 1998 18 8505 8514 10.1523/JNEUROSCI.18-20-08505.1998
Gassmann M. Shaban H. Vigot R. Sansig G. Haller C. Barbieri S. Humeau Y. Schuler V. Müller M. Kinzel B. et al. Redistribution of GABAB(1) Protein and Atypical GABAB Responses in GABAB(2)-Deficient Mice J. Neurosci. 2004 24 6086 6097 10.1523/JNEUROSCI.5635-03.2004
Schuler V. Lüscher C. Blanchet C. Klix N. Sansig G. Klebs K. Schmutz M. Heid J. Gentry C. Urban L. et al. Epilepsy, Hyperalgesia, Impaired Memory, and Loss of Pre- and Postsynaptic GABA(B) Responses in Mice Lacking GABA(B(1)) Neuron 2001 31 47 58 10.1016/S0896-6273(01)00345-2
Cope D.W. Di Giovanni G. Fyson S.J. Orbán G. Errington A.C. Lrincz M.L. Gould T.M. Carter D.A. Crunelli V. Enhanced Tonic GABAA Inhibition in Typical Absence Epilepsy Nat. Med. 2009 15 1392 1398 10.1038/nm.2058 19966779
Kim D. Song I. Keum S. Lee T. Jeong M.J. Kim S.S. McEnery M.W. Shin H.S. Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ Channels Neuron 2001 31 35 45 10.1016/S0896-6273(01)00343-9 11498049
Ernst W.L. Zhang Y. Yoo J.W. Ernst S.J. Noebels J.L. Genetic Enhancement of Thalamocortical Network Activity by Elevating Alpha 1g-Mediated Low-Voltage-Activated Calcium Current Induces Pure Absence Epilepsy J. Neurosci. 2009 29 1615 1625 10.1523/JNEUROSCI.2081-08.2009 19211869
Zhang Y. Mori M. Burgess D.L. Noebels J.L. Mutations in High-Voltage-Activated Calcium Channel Genes Stimulate Low-Voltage-Activated Currents in Mouse Thalamic Relay Neurons J. Neurosci. 2002 22 6362 6371 10.1523/JNEUROSCI.22-15-06362.2002
Song I. Kim D. Choi S. Sun M. Kim Y. Shin H.S. Role of the Alpha1G T-Type Calcium Channel in Spontaneous Absence Seizures in Mutant Mice J. Neurosci. 2004 24 5249 5257 10.1523/JNEUROSCI.5546-03.2004
Lee S.E. Lee J. Latchoumane C. Lee B. Oh S.J. Saud Z.A. Park C. Sun N. Cheong E. Chen C.C. et al. Rebound Burst Firing in the Reticular Thalamus Is Not Essential for Pharmacological Absence Seizures in Mice Proc. Natl. Acad. Sci. USA 2014 111 11828 11833 10.1073/pnas.1408609111
Huang Z. Walker M.C. Shah M.M. Loss of Dendritic HCN1 Subunits Enhances Cortical Excitability and Epileptogenesis J. Neurosci. 2009 29 10979 10988 10.1523/JNEUROSCI.1531-09.2009
Santoro B. Lee J.Y. Englot D.J. Gildersleeve S. Piskorowski R.A. Siegelbaum S.A. Winawer M.R. Blumenfeld H. Increased Seizure Severity and Seizure-Related Death in Mice Lacking HCN1 Channels Epilepsia 2010 51 1624 1627 10.1111/j.1528-1167.2010.02554.x
Nishitani A. Kunisawa N. Sugimura T. Sato K. Yoshida Y. Suzuki T. Sakuma T. Yamamoto T. Asano M. Saito Y. et al. Loss of HCN1 Subunits Causes Absence Epilepsy in Rats Brain Res. 2019 1706 209 217 10.1016/j.brainres.2018.11.004
Frankel W.N. Mahaffey C.L. McGarr T.C. Beyer B.J. Letts V.A. Unraveling Genetic Modifiers in the Gria4 Mouse Model of Absence Epilepsy PLoS Genet. 2014 10 1004454 10.1371/journal.pgen.1004454
Ludwig A. Budde T. Stieber J. Moosmang S. Wahl C. Holthoff K. Langebartels A. Wotjak C. Munsch T. Zong X. et al. Absence Epilepsy and Sinus Dysrhythmia in Mice Lacking the Pacemaker Channel HCN2 EMBO J. 2003 22 216 224 10.1093/emboj/cdg032 12514127
Ying S.W. Jia F. Abbas S.Y. Hofmann F. Ludwig A. Goldstein P.A. Dendritic HCN2 Channels Constrain Glutamate-Driven Excitability in Reticular Thalamic Neurons J. Neurosci. 2007 27 8719 8732 10.1523/JNEUROSCI.1630-07.2007
Zobeiri M. Chaudhary R. Blaich A. Rottmann M. Herrmann S. Meuth P. Bista P. Kanyshkova T. Lüttjohann A. Narayanan V. et al. The Hyperpolarization-Activated HCN4 Channel Is Important for Proper Maintenance of Oscillatory Activity in the Thalamocortical System Cereb. Cortex 2019 29 2291 2304 10.1093/cercor/bhz047 30877792
Miao Q.L. Herlitze S. Mark M.D. Noebels J.L. Adult Loss of Cacna1a in Mice Recapitulates Childhood Absence Epilepsy by Distinct Thalamic Bursting Mechanisms Brain 2020 143 161 174 10.1093/brain/awz365
Bomben V.C. Aiba I. Qian J. Mark M.D. Herlitze S. Noebels J.L. Isolated P/Q Calcium Channel Deletion in Layer VI Corticothalamic Neurons Generates Absence Epilepsy J. Neurosci. 2016 36 405 418 10.1523/JNEUROSCI.2555-15.2016
Gawel K. Turski W.A. van der Ent W. Mathai B.J. Kirstein-Smardzewska K.J. Simonsen A. Esguerra C.V. Phenotypic Characterization of Larval Zebrafish (Danio Rerio) with Partial Knockdown of the Cacna1a Gene Mol. Neurobiol. 2020 57 1904 1916 10.1007/s12035-019-01860-x 31875924
Bell S.M. Schreiner C.M. Schultheis P.J. Miller M.L. Evans R.L. Vorhees C.V. Shull G.E. Scott W.J. Targeted Disruption of the Murine Nhe1 Locus Induces Ataxia, Growth Retardation, and Seizures Am. J. Physiol. 1999 276 C788 C795 10.1152/ajpcell.1999.276.4.C788
Xia Y. Zhao P. Xue J. Gu X.Q. Sun X. Yao H. Haddad G.G. Na+ Channel Expression and Neuronal Function in the Na+/H+ Exchanger 1 Null Mutant Mouse J. Neurophysiol. 2003 89 229 236 10.1152/jn.00488.2002
Campos-Rodriguez C. Palmer D. Forcelli P.A. Optogenetic Stimulation of the Superior Colliculus Suppresses Genetic Absence Seizures Brain 2023 146 4320 4335 10.1093/brain/awad166
Hyder S.K. Lazarini-Lopes W. Toib J. Williams G. Sukharev A. Forcelli P.A. Optogenetic Stimulation of Dorsal Striatum Bidirectionally Controls Seizures bioRxiv 2024 10.1073/pnas.2419178122
Kros L. Eelkman Rooda O.H.J. Spanke J.K. Alva P. Van Dongen M.N. Karapatis A. Tolner E.A. Strydis C. Davey N. Winkelman B.H.J. et al. Cerebellar Output Controls Generalized Spike-and-Wave Discharge Occurrence Ann. Neurol. 2015 77 1027 1049 10.1002/ana.24399 25762286
Schwitalla J.C. Pakusch J. Mücher B. Brückner A. Depke D.A. Fenzl T. De Zeeuw C.I. Kros L. Hoebeek F.E. Mark M.D. Controlling Absence Seizures from the Cerebellar Nuclei via Activation of the Gq Signaling Pathway Cell Mol. Life Sci. 2022 79 197 10.1007/s00018-022-04221-5 35305155
Dong P. Bakhurin K. Li Y. Mikati M.A. Cui J. Grill W.M. Yin H.H. Yang H. Attenuating Midline Thalamus Bursting to Mitigate Absence Epilepsy Proc. Natl. Acad. Sci. USA 2024 121 e2403763121 10.1073/pnas.2403763121 38968111
Ozgur M. Özyurt M.G. Arkan S. Cavdar S. The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats Ann. Neurosci. 2022 29 53 61 10.1177/09727531211072423
Panthi S. Leitch B. The Impact of Silencing Feed-Forward Parvalbumin-Expressing Inhibitory Interneurons in the Cortico-Thalamocortical Network on Seizure Generation and Behaviour Neurobiol. Dis. 2019 132 104610 10.1016/j.nbd.2019.104610
Panthi S. Leitch B. Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures Front. Cell Neurosci. 2021 15 688905 10.3389/fncel.2021.688905
Abdelaal M.S. Midorikawa M. Suzuki T. Kobayashi K. Takata N. Miyata M. Mimura M. Tanaka K.F. Dysfunction of Parvalbumin-Expressing Cells in the Thalamic Reticular Nucleus Induces Cortical Spike-and-Wave Discharges and an Unconscious State Brain Commun. 2022 4 fcac010 10.1093/braincomms/fcac010
Stevelink R. Koeleman B.P.C. Sander J.W. Jansen F.E. Braun K.P.J. Refractory Juvenile Myoclonic Epilepsy: A Meta-Analysis of Prevalence and Risk Factors Eur. J. Neurol. 2019 26 856 864 10.1111/ene.13811
Silvennoinen K. de Lange N. Zagaglia S. Balestrini S. Androsova G. Wassenaar M. Auce P. Avbersek A. Becker F. Berghuis B. et al. Comparative Effectiveness of Antiepileptic Drugs in Juvenile Myoclonic Epilepsy Epilepsia Open 2019 4 420 430 10.1002/epi4.12349
Meencke H. Veith G. The Relevance of Slight Migrational Disturbances (Microdysgenesis) to the Etiology of the Epilepsies Delgado-Escueta A.V. Wilson W.A. Olsen R.W. Porter R.J. Advances in Neurology Lippincott Williams and Wilkins Philadelphia, PA, USA 1999 Volume 79
Gilsoul M. Grisar T. Delgado-Escueta A.V. de Nijs L. Lakaye B. Subtle Brain Developmental Abnormalities in the Pathogenesis of Juvenile Myoclonic Epilepsy Front. Cell Neurosci. 2019 13 00433 10.3389/fncel.2019.00433
Caciagli L. Wandschneider B. Xiao F. Vollmar C. Centeno M. Vos S.B. Trimmel K. Sidhu M.K. Thompson P.J. Winston G.P. et al. Abnormal Hippocampal Structure and Function in Juvenile Myoclonic Epilepsy and Unaffected Siblings Brain 2019 142 2670 2687 10.1093/brain/awz215 31365054
Bajic D. Ewald U. Raininko R. Hippocampal Development at Gestation Weeks 23 to 36. An Ultrasound Study on Preterm Neonates Neuroradiology 2010 52 489 494 10.1007/s00234-010-0673-x
Lin J.J. Dabbs K. Riley J.D. Jones J.E. Jackson D.C. Hsu D.A. Stafstrom C.E. Seidenberg M. Hermann B.P. Neurodevelopment in New-Onset Juvenile Myoclonic Epilepsy over the First 2 Years Ann. Neurol. 2014 76 660 668 10.1002/ana.24240
Perani S. Tierney T.M. Centeno M. Shamshiri E.A. Yaakub S.N. O’Muircheartaigh J. Carmichael D.W. Richardson M.P. Thalamic Volume Reduction in Drug-Naive Patients with New-Onset Genetic Generalized Epilepsy Epilepsia 2018 59 226 234 10.1111/epi.13955
Ekmekci B. Bulut H.T. Gümüştaş F. Yıldırım A. Kuştepe A. The Relationship between White Matter Abnormalities and Cognitive Functions in New-Onset Juvenile Myoclonic Epilepsy Epilepsy Behav. 2016 62 166 170 10.1016/j.yebeh.2016.07.015
Wight J.E. Nguyen V.H. Medina M.T. Patterson C. Durón R.M. Molina Y. Lin Y.C. Martínez-Juárez I.E. Ochoa A. Jara-Prado A. et al. Chromosome Loci Vary by Juvenile Myoclonic Epilepsy Subsyndromes: Linkage and Haplotype Analysis Applied to Epilepsy and EEG 3.5-6.0 Hz Polyspike Waves Mol. Genet. Genomic Med. 2016 4 197 210 10.1002/mgg3.195 27066514
Killam E.K. Stark L.G. Killam K.F. Photic-Stimulation in Three Species of Baboons Life Sci. 1967 6 1569 1574 10.1016/0024-3205(67)90165-8
Szabó C.Á. Knape D.K. Leland M.M. Cwikla J.D. Williams-Blangero S. Williams T.J. Epidemiology and Characterization of Seizures in a Pedigreed Baboon Colony Comp. Med. 2012 62 535 538
Croll L. Szabo C.A. Abou-Madi N. Devinsky O. Epilepsy in Nonhuman Primates Epilepsia 2019 60 1526 1538 10.1111/epi.16089
Young N.A. Szabó C.A. Phelix C.F. Flaherty D.K. Balaram P. Foust-Yeoman K.B. Collins C.E. Kaas J.H. Epileptic Baboons Have Lower Numbers of Neurons in Specific Areas of Cortex Proc. Natl. Acad. Sci. USA 2013 110 19107 19112 10.1073/pnas.1318894110 24191031
Szabó C.Á. Salinas F.S. Voxel-Based Morphometry in Epileptic Baboons: Parallels to Human Juvenile Myoclonic Epilepsy Epilepsy Res. 2016 124 34 39 10.1016/j.eplepsyres.2016.05.009
Kos M.Z. Carless M.A. Blondell L. Leland M.M. Knape K.D. Göring H.H.H. Szabó C.Á. Whole Genome Sequence Data from Captive Baboons Implicate RBFOX1 in Epileptic Seizure Risk Front. Genet. 2021 12 714282 10.3389/fgene.2021.714282 34490042
Gehman L.T. Stoilov P. Maguire J. Damianov A. Lin C.H. Shiue L. Ares M. Mody I. Black D.L. The Splicing Regulator Rbfox1 (A2BP1) Controls Neuronal Excitation in the Mammalian Brain Nat. Genet. 2011 43 706 711 10.1038/ng.841
Vuong C.K. Wei W. Lee J.A. Lin C.H. Damianov A. de la Torre-Ubieta L. Halabi R. Otis K.O. Martin K.C. O’Dell T.J. et al. Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific VSNARE Vamp1 Neuron 2018 98 127 141.e7 10.1016/j.neuron.2018.03.008 29621484
Wamsley B. Jaglin X.H. Favuzzi E. Quattrocolo G. Nigro M.J. Yusuf N. Khodadadi-Jamayran A. Rudy B. Fishell G. Rbfox1 Mediates Cell-Type-Specific Splicing in Cortical Interneurons Neuron 2018 100 846 859.e7 10.1016/j.neuron.2018.09.026
Smemo S. Tena J.J. Kim K.H. Gamazon E.R. Sakabe N.J. Gómez-Marín C. Aneas I. Credidio F.L. Sobreira D.R. Wasserman N.F. et al. Obesity-Associated Variants within FTO Form Long-Range Functional Connections with IRX3 Nature 2014 507 371 375 10.1038/nature13138
Wielaender F. Sarviaho R. James F. Hytönen M.K. Cortez M.A. Kluger G. Koskinen L.L.E. Arumilli M. Kornberg M. Bathen-Noethen A. et al. Generalized Myoclonic Epilepsy with Photosensitivity in Juvenile Dogs Caused by a Defective DIRAS Family GTPase 1 Proc. Natl. Acad. Sci. USA 2017 114 2669 2674 10.1073/pnas.1614478114
Tada M. Gengyo-Ando K. Kobayashi T. Fukuyama M. Mitani S. Kontani K. Katada T. Neuronally Expressed Ras-Family GTPase Di-Ras Modulates Synaptic Activity in Caenorhabditis Elegans Genes. Cells 2012 17 778 789 10.1111/j.1365-2443.2012.01627.x
Yeh C.W. Hsu L.S. Zebrafish Diras1 Promoted Neurite Outgrowth in Neuro-2a Cells and Maintained Trigeminal Ganglion Neurons In Vivo via Rac1-Dependent Pathway Mol. Neurobiol. 2016 53 6594 6607 10.1007/s12035-015-9550-2
Cossette P. Liu L. Brisebois K. Dong H. Lortie A. Vanasse M. Saint-Hilaire J.M. Carmant L. Verner A. Lu W.Y. et al. Mutation of GABRA1 in an Autosomal Dominant Form of Juvenile Myoclonic Epilepsy Nat. Genet. 2002 31 184 189 10.1038/ng885 11992121
Gallagher M.J. Ding L. Maheshwari A. Macdonald R.L. The GABAA Receptor Alpha1 Subunit Epilepsy Mutation A322D Inhibits Transmembrane Helix Formation and Causes Proteasomal Degradation Proc. Natl. Acad. Sci. USA 2007 104 12999 13004 10.1073/pnas.0700163104 17670950
Ding L. Feng H.J. Macdonald R.L. Botzolakis E.J. Hu N. Gallagher M.J. GABA(A) Receptor Alpha1 Subunit Mutation A322D Associated with Autosomal Dominant Juvenile Myoclonic Epilepsy Reduces the Expression and Alters the Composition of Wild Type GABA(A) Receptors J. Biol. Chem. 2010 285 26390 26405 10.1074/jbc.M110.142299 20551311
Arain F.M. Boyd K.L. Gallagher M.J. Decreased Viability and Absence-like Epilepsy in Mice Lacking or Deficient in the GABAA Receptor α1 Subunit Epilepsia 2012 53 e161 e165 10.1111/j.1528-1167.2012.03596.x
Arain F. Zhou C. Ding L. Zaidi S. Gallagher M.J. The Developmental Evolution of the Seizure Phenotype and Cortical Inhibition in Mouse Models of Juvenile Myoclonic Epilepsy Neurobiol. Dis. 2015 82 164 175 10.1016/j.nbd.2015.05.016
Samarut É. Swaminathan A. Riché R. Liao M. Hassan-Abdi R. Renault S. Allard M. Dufour L. Cossette P. Soussi-Yanicostas N. et al. γ-Aminobutyric Acid Receptor Alpha 1 Subunit Loss of Function Causes Genetic Generalized Epilepsy by Impairing Inhibitory Network Neurodevelopment Epilepsia 2018 59 2061 2074 10.1111/epi.14576
Suzuki T. Delgado-Escueta V.A. Aguan K. Alonso M.E. Shi J. Haras Y. Nishidas M. Numata T. Medina M.T. Takeuchi T. et al. Mutations in EFHC1 Cause Juvenile Myoclonic Epilepsy Nat. Genet. 2004 36 842 849 10.1038/ng1393
Annesi F. Gambardella A. Michelucci R. Bianchi A. Marini C. Canevini M.P. Capovilla G. Elia M. Buti D. Chifari R. et al. Mutational Analysis of EFHC1 Gene in Italian Families with Juvenile Myoclonic Epilepsy Epilepsia 2007 48 1686 1690 10.1111/j.1528-1167.2007.01173.x
Bailey J.N. Patterson C. De Nijs L. Durón R.M. Nguyen V.H. Tanaka M. Medina M.T. Jara-Prado A. Martínez-Juárez I.E. Ochoa A. et al. EFHC1 Variants in Juvenile Myoclonic Epilepsy: Reanalysis According to NHGRI and ACMG Guidelines for Assigning Disease Causality Genet. Med. 2017 19 144 156 10.1038/gim.2016.86
Ikeda K. Brown J.A. Yagi T. Norrander J.M. Hirono M. Eccleston E. Kamiya R. Linck R.W. Rib72, a Conserved Protein Associated with the Ribbon Compartment of Flagellar A-Microtubules and Potentially Involved in the Linkage between Outer Doublet Microtubules J. Biol. Chem. 2003 278 7725 7734 10.1074/jbc.M210751200
Ikeda T. Ikeda K. Enomoto M. Park M.K. Hirono M. Kamiya R. The Mouse Ortholog of EFHC1 Implicated in Juvenile Myoclonic Epilepsy Is an Axonemal Protein Widely Conserved among Organisms with Motile Cilia and Flagella FEBS Lett. 2005 579 819 822 10.1016/j.febslet.2004.12.070 15670853
Ma M. Stoyanova M. Rademacher G. Dutcher S.K. Brown A. Zhang R. Structure of the Decorated Ciliary Doublet Microtubule Cell 2019 179 909 922.e12 10.1016/j.cell.2019.09.030
Stoddard D. Zhao Y. Bayless B.A. Gui L. Louka P. Dave D. Suryawanshi S. Tomasi R.F.X. Dupuis-Williams P. Baroud C.N. et al. Tetrahymena RIB72A and RIB72B Are Microtubule Inner Proteins in the Ciliary Doublet Microtubules Mol. Biol. Cell 2018 29 2566 2577 10.1091/mbc.E18-06-0405 30133348
Suzuki T. Miyamoto H. Nakahari T. Inoue I. Suemoto T. Jiang B. Hirota Y. Itohara S. Saido T.C. Tsumoto T. et al. Efhc1 Deficiency Causes Spontaneous Myoclonus and Increased Seizure Susceptibility Hum. Mol. Genet. 2009 18 1099 1109 10.1093/hmg/ddp006 19147686
Loucks C.M. Park K. Walker D.S. McEwan A.H. Timbers T.A. Ardiel E.L. Grundy L.J. Li C. Johnson J.L. Kennedy J. et al. EFHC1, Implicated in Juvenile Myoclonic Epilepsy, Functions at the Cilium and Synapse to Modulate Dopamine Signaling Elife 2019 8 37271 10.7554/eLife.37271
Rossetto M.G. Zanarella E. Orso G. Scorzeto M. Megighian A. Kumar V. Delgado-escueta A.V. Daga A. Defhc1.1, a Homologue of the Juvenile Myoclonic Gene EFHC1, Modulates Architecture and Basal Activity of the Neuromuscular Junction in Drosophila Hum. Mol. Genet. 2011 20 4248 4257 10.1093/hmg/ddr352
Zhao Y. Shi J. Winey M. Klymkowsky M.W. Identifying Domains of EFHC1 Involved in Ciliary Localization, Ciliogenesis, and the Regulation of Wnt Signaling Dev. Biol. 2016 411 257 265 10.1016/j.ydbio.2016.01.004
de Nijs L. Lakaye B. Coumans B. Léon C. Ikeda T. Delgado-Escueta A.V. Grisar T. Chanas G. EFHC1, a Protein Mutated in Juvenile Myoclonic Epilepsy, Associates with the Mitotic Spindle through Its N-Terminus Exp. Cell Res. 2006 312 2872 2879 10.1016/j.yexcr.2006.05.011
De Nijs L. Léon C. Nguyen L. Loturco J.J. Delgado-Escueta A.V. Grisar T. Lakaye B. EFHC1 Interacts with Microtubules to Regulate Cell Division and Cortical Development Nat. Neurosci. 2009 12 1266 1274 10.1038/nn.2390
Raju P.K. Satishchandra P. Nayak S. Iyer V. Sinha S. Anand A. Microtubule-Associated Defects Caused by EFHC1 Mutations in Juvenile Myoclonic Epilepsy Hum. Mutat. 2017 38 816 826 10.1002/humu.23221
De Nijs L. Wolkoff N. Coumans B. Delgado-Escueta A.V. Grisar T. Lakaye B. Mutations of EFHC1, Linked to Juvenile Myoclonic Epilepsy, Disrupt Radial and Tangential Migrations during Brain Development Hum. Mol. Genet. 2012 21 5106 5117 10.1093/hmg/dds356 22926142
Wolkoff N. Influence of Mutated Forms of EFHC1 (or Myoclonin 1), a Protein Involved in Juvenile Myoclonic Epilepsy, on Cerebral Corticogenesis Ph.D. Thesis University of Liège Liège, Belgium 2014
Linck R. Fu X. Lin J. Ouch C. Schefter A. Steffen W. Warren P. Nicastro D. Insights into the Structure and Function of Ciliary and Flagellar Doublet Microtubules: Tektins, Ca2+-Binding Proteins, and Stable Protofilaments J. Biol. Chem. 2014 289 17427 17444 10.1074/jbc.M114.568949 24794867
Yang S.K. Kubo S. Black C.S. Peri K. Dai D. Legal T. Valente-Paterno M. Gaertig J. Bui K.H. Effect of α-Tubulin Acetylation on the Doublet Microtubule Structure Elife 2024 12 92219 10.7554/eLife.92219.3
Fabritius A.S. Bayless B.A. Li S. Stoddard D. Heydeck W. Ebmeier C.C. Anderson L. Gunnels T. Nachiappan C. Whittall J.B. et al. Proteomic Analysis of Microtubule Inner Proteins (MIPs) in Rib72 Null Tetrahymena Cells Reveals Functional MIPs Mol. Biol. Cell 2021 32 br8 10.1091/mbc.E20-12-0786
Chakraborty S. Martinez-Sanchez A. Beck F. Toro-Nahuelpan M. Hwang I.-Y. Noh K.-M. Baumeister W. Mahamid J. Cryo-Electron Tomography Suggests Tubulin Chaperones Form a Subset of Microtubule Lumenal Particles with a Role in Maintaining Neuronal Microtubules bioRxiv 2022 10.1101/2022.07.28.501854
Tsuji C. Dodding M.P. Lumenal Components of Cytoplasmic Microtubules Biochem. Soc. Trans. 2022 50 1953 1962 10.1042/BST20220851
Kar S. Fan J. Smith M.J. Goedert M. Amos L.A. Repeat Motifs of Tau Bind to the Insides of Microtubules in the Absence of Taxol EMBO J. 2003 22 70 77 10.1093/emboj/cdg001 12505985
de Nijs L. Wolkoff N. Grisar T. Lakaye B. Juvenile Myoclonic Epilepsy as a Possible Neurodevelopmental Disease: Role of EFHC1 or Myoclonin1 Epilepsy Behav. 2013 28 (Suppl. S1) S58 S60 10.1016/j.yebeh.2012.06.034
Fame R.M. Lehtinen M.K. Emergence and Developmental Roles of the Cerebrospinal Fluid System Dev. Cell 2020 52 261 275 10.1016/j.devcel.2020.01.027
Chikina A.S. Zholudeva A.O. Lomakina M.E. Kireev I.I. Dayal A.A. Minin A.A. Maurin M. Svitkina T.M. Alexandrova A.Y. Plasma Membrane Blebbing Is Controlled by Subcellular Distribution of Vimentin Intermediate Filaments Cells 2024 13 105 10.3390/cells13010105
Fourriere L. Jimenez A.J. Perez F. Boncompain G. The Role of Microtubules in Secretory Protein Transport J. Cell Sci. 2020 133 237016 10.1242/jcs.237016 31996399
Courtney Y. Head J.P. Yimer E.D. Dani N. Shipley F.B. Libermann T.A. Lehtinen M.K. A Choroid Plexus Apocrine Secretion Mechanism Shapes CSF Proteome and Embryonic Brain Development bioRxiv 2024 10.1101/2024.01.08.574486
Jessen N.A. Munk A.S.F. Lundgaard I. Nedergaard M. The Glymphatic System: A Beginner’s Guide Neurochem. Res. 2015 40 2583 2599 10.1007/s11064-015-1581-6 25947369
Christensen J. Yamakawa G.R. Shultz S.R. Mychasiuk R. Is the Glymphatic System the Missing Link between Sleep Impairments and Neurological Disorders? Examining the Implications and Uncertainties Prog. Neurobiol. 2021 198 101917 10.1016/j.pneurobio.2020.101917
Lundgaard I. Wang W. Eberhardt A. Vinitsky H.S. Reeves B.C. Peng S. Lou N. Hussain R. Nedergaard M. Beneficial Effects of Low Alcohol Exposure, but Adverse Effects of High Alcohol Intake on Glymphatic Function Sci. Rep. 2018 8 2246 10.1038/s41598-018-20424-y
Lee H.J. Lee D.A. Shin K.J. Park K.M. Glymphatic System Dysfunction in Patients with Juvenile Myoclonic Epilepsy J. Neurol. 2022 269 2133 2139 10.1007/s00415-021-10799-w
Dibbens L.M. Feng H.J. Richards M.C. Harkin L.A. Hodgson B.L. Scott D. Jenkins M. Petrou S. Sutherland G.R. Scheffer I.E. et al. GABRD Encoding a Protein for Extra- or Peri-Synaptic GABAA Receptors Is a Susceptibility Locus for Generalized Epilepsies Hum. Mol. Genet. 2004 13 1315 1319 10.1093/hmg/ddh146
Feng H.J. Kang J.Q. Song L. Dibbens L. Mulley J. Macdonald R.L. Delta Subunit Susceptibility Variants E177A and R220H Associated with Complex Epilepsy Alter Channel Gating and Surface Expression of Alpha4beta2delta GABAA Receptors J. Neurosci. 2006 26 1499 1506 10.1523/JNEUROSCI.2913-05.2006
Glykys J. Mann E.O. Mody I. Which GABA(A) Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus? J. Neurosci. 2008 28 1421 1426 10.1523/JNEUROSCI.4751-07.2008
Cope D.W. Hughes S.W. Crunelli V. GABAA Receptor-Mediated Tonic Inhibition in Thalamic Neurons J. Neurosci. 2005 25 11553 11563 10.1523/JNEUROSCI.3362-05.2005
Spigelman I. Li Z. Banerjee P.K. Mihalek R.M. Homanics G.E. Olsen R.W. Behavior and Physiology of Mice Lacking the GABAA-Receptor Delta Subunit Epilepsia 2002 43 (Suppl. S5) 3 8 10.1046/j.1528-1157.43.s.5.8.x 12121286
Lee V. Maguire J. Impact of Inhibitory Constraint of Interneurons on Neuronal Excitability J. Neurophysiol. 2013 110 2520 2535 10.1152/jn.00047.2013 24027099
Ahring P.K. Liao V.W.Y. Gardella E. Johannesen K.M. Krey I. Selmer K.K. Stadheim B.F. Davis H. Peinhardt C. Koko M. et al. Gain-of-Function Variants in GABRD Reveal a Novel Pathway for Neurodevelopmental Disorders and Epilepsy Brain 2022 145 1299 1309 10.1093/brain/awab391
Kapoor A. Satishchandra P. Ratnapriya R. Reddy R. Kadandale J. Shankar S.K. Anand A. An Idiopathic Epilepsy Syndrome Linked to 3q13.3-Q21 and Missense Mutations in the Extracellular Calcium Sensing Receptor Gene Ann. Neurol. 2008 64 158 167 10.1002/ana.21428
Junjie N. Lina Q. Analysis of CASR Gene Variant in a Child with Idiopathic Epilepsy and Autism Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 39 309 311 10.3760/CMA.J.CN511374-20201209-00862
Stepanchick A. McKenna J. McGovern O. Huang Y. Breitwieser G.E. Calcium Sensing Receptor Mutations Implicated in Pancreatitis and Idiopathic Epilepsy Syndrome Disrupt an Arginine-Rich Retention Motif Cell Physiol. Biochem. 2010 26 363 374 10.1159/000320560 20798521
Liu X.L. Lu Y.S. Gao J.Y. Marshall C. Xiao M. Miao D.S. Karaplis A. Goltzman D. Ding J. Calcium Sensing Receptor Absence Delays Postnatal Brain Development via Direct and Indirect Mechanisms Mol. Neurobiol. 2013 48 590 600 10.1007/s12035-013-8448-0
Ruat M. Traiffort E. Roles of the Calcium Sensing Receptor in the Central Nervous System Best Pract. Res. Clin. Endocrinol. Metab. 2013 27 429 442 10.1016/j.beem.2013.03.001
Marques S. Zeisel A. Codeluppi S. Van Bruggen D. Falcão A.M. Xiao L. Li H. Häring M. Hochgerner H. Romanov R.A. et al. Oligodendrocyte Heterogeneity in the Mouse Juvenile and Adult Central Nervous System Science 2016 352 1326 1329 10.1126/science.aaf6463
Vizard T.N. O’Keeffe G.W. Gutierrez H. Kos C.H. Riccardi D. Davies A.M. Regulation of Axonal and Dendritic Growth by the Extracellular Calcium-Sensing Receptor Nat. Neurosci. 2008 11 285 291 10.1038/nn2044
Pal D.K. Evgrafov O.V. Tabares P. Zhang F. Durner M. Greenberg D.A. BRD2 (RING3) Is a Probable Major Susceptibility Gene for Common Juvenile Myoclonic Epilepsy Am. J. Hum. Genet. 2003 73 261 270 10.1086/377006
Pathak S. Miller J. Morris E.C. Stewart W.C.L. Greenberg D.A. DNA Methylation of the BRD2 Promoter Is Associated with Juvenile Myoclonic Epilepsy in Caucasians Epilepsia 2018 59 1011 1019 10.1111/epi.14058 29608786
Schulz H. Ruppert A.K. Zara F. Madia F. Iacomino M. Vari M.S. Balagura G. Minetti C. Striano P. Bianchi A. et al. No Evidence for a BRD2 Promoter Hypermethylation in Blood Leukocytes of Europeans with Juvenile Myoclonic Epilepsy Epilepsia 2019 60 e31 e36 10.1111/epi.14657 30719712
Cavalleri G.L. Walley N.M. Soranzo N. Mulley J. Doherty C.P. Kapoor A. Depondt C. Lynch J.M. Scheffer I.E. Heils A. et al. A Multicenter Study of BRD2 as a Risk Factor for Juvenile Myoclonic Epilepsy Epilepsia 2007 48 706 712 10.1111/j.1528-1167.2007.00977.x
Hnilicová J. Hozeifi S. Stejskalová E. Dušková E. Poser I. Humpolíčková J. Hof M. Staněk D. The C-Terminal Domain of Brd2 Is Important for Chromatin Interaction and Regulation of Transcription and Alternative Splicing Mol. Biol. Cell 2013 24 3557 3568 10.1091/mbc.e13-06-0303
Shang E. Wang X. Wen D. Greenberg D.A. Wolgemuth D.J. Double Bromodomain-Containing Gene Brd2 Is Essential for Embryonic Development in Mouse Dev. Dyn. 2009 238 908 917 10.1002/dvdy.21911 19301389
Velíšek L. Shang E. Velíšková J. Chachua T. Macchiarulo S. Maglakelidze G. Wolgemuth D.J. Greenberg D.A. GABAergic Neuron Deficit as an Idiopathic Generalized Epilepsy Mechanism: The Role of BRD2 Haploinsufficiency in Juvenile Myoclonic Epilepsy PLoS ONE 2011 6 23656 10.1371/journal.pone.0023656
McCarthy E. Shakil F. Saint Ange P. Morris Cameron E. Miller J. Pathak S. Greenberg D.A. Velíšková J. Velíšek L. Developmental Decrease in Parvalbumin-Positive Neurons Precedes Increase in Flurothyl-Induced Seizure Susceptibility in the Brd2+/- Mouse Model of Juvenile Myoclonic Epilepsy Epilepsia 2020 61 892 902 10.1111/epi.16499
Murphy T. Melville H. Fradkin E. Bistany G. Branigan G. Olsen K. Comstock C.R. Hanby H. Garbade E. DiBenedetto A.J. Knockdown of Epigenetic Transcriptional Co-Regulator Brd2a Disrupts Apoptosis and Proper Formation of Hindbrain and Midbrain-Hindbrain Boundary (MHB) Region in Zebrafish Mech. Dev. 2017 146 10 30 10.1016/j.mod.2017.05.003
Branigan G.L. Olsen K.S. Burda I. Haemmerle M.W. Ho J. Venuto A. D’antonio N.D. Briggs I.E. Dibenedetto A.J. Zebrafish Paralogs Brd2a and Brd2b Are Needed for Proper Circulatory, Excretory and Central Nervous System Formation and Act as Genetic Antagonists during Development J. Dev. Biol. 2021 9 46 10.3390/jdb9040046
Bailey J.N. de Nijs L. Bai D. Suzuki T. Miyamoto H. Tanaka M. Patterson C. Lin Y.-C. Medina M.T. Alonso M.E. et al. Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy N. Engl. J. Med. 2018 378 1018 1028 10.1056/NEJMoa1700175 29539279
Lahiry P. Wang J. Robinson J.F. Turowec J.P. Litchfield D.W. Lanktree M.B. Gloor G.B. Puffenberger E.G. Strauss K.A. Martens M.B. et al. A Multiplex Human Syndrome Implicates a Key Role for Intestinal Cell Kinase in Development of Central Nervous, Skeletal, and Endocrine Systems Am. J. Hum. Genet. 2009 84 134 147 10.1016/j.ajhg.2008.12.017 19185282
Taylor S.P. Bosakova M.K. Varecha M. Balek L. Barta T. Trantirek L. Jelinkova I. Duran I. Vesela I. Forlenza K.N. et al. An Inactivating Mutation in Intestinal Cell Kinase, ICK, Impairs Hedgehog Signalling and Causes Short Rib-Polydactyly Syndrome Hum. Mol. Genet. 2016 25 3998 4011 10.1093/hmg/ddw240
Fu Z. Gailey C.D. Wang E.J. Brautigan D.L. Ciliogenesis Associated Kinase 1: Targets and Functions in Various Organ Systems FEBS Lett. 2019 593 2990 3002 10.1002/1873-3468.13600
Fu Z. Larson K.A. Chitta R.K. Parker S.A. Turk B.E. Lawrence M.W. Kaldis P. Galaktionov K. Cohn S.M. Shabanowitz J. et al. Identification of Yin-Yang Regulators and a Phosphorylation Consensus for Male Germ Cell-Associated Kinase (MAK)-Related Kinase Mol. Cell Biol. 2006 26 8639 8654 10.1128/MCB.00816-06
Bosakova M.K. Nita A. Gregor T. Varecha M. Gudernova I. Fafilek B. Barta T. Basheer N. Abraham S.P. Balek L. et al. Fibroblast Growth Factor Receptor Influences Primary Cilium Length through an Interaction with Intestinal Cell Kinase Proc. Natl. Acad. Sci. USA 2019 116 4316 4325 10.1073/pnas.1800338116
Tong Y. Park S. Wu D. Harris T.E. Moskaluk C.A. Brautigan D.L. Fu Z. Modulation of GSK3β Autoinhibition by Thr-7 and Thr-8 FEBS Lett. 2018 592 537 546 10.1002/1873-3468.12990
Oh Y.S. Wang E.J. Gailey C.D. Brautigan D.L. Allen B.L. Fu Z. Ciliopathy-Associated Protein Kinase ICK Requires Its Non-Catalytic Carboxyl-Terminal Domain for Regulation of Ciliogenesis Cells 2019 8 677 10.3390/cells8070677 31277411
Wu D. Chapman J.R. Wang L. Harris T.E. Shabanowitz J. Hunt D.F. Fu Z. Intestinal Cell Kinase (ICK) Promotes Activation of MTOR Complex 1 (MTORC1) through Phosphorylation of Raptor Thr-908 J. Biol. Chem. 2012 287 12510 12519 10.1074/jbc.M111.302117
Tsutsumi R. Chaya T. Tsujii T. Furukawa T. The Carboxyl-Terminal Region of SDCCAG8 Comprises a Functional Module Essential for Cilia Formation as Well as Organ Development and Homeostasis J. Biol. Chem. 2022 298 101686 10.1016/j.jbc.2022.101686
Fu Z. Schroeder M.J. Shabanowitz J. Kaldis P. Togawa K. Rustgi A.K. Hunt D.F. Sturgill T.W. Activation of a Nuclear Cdc2-Related Kinase within a Mitogen-Activated Protein Kinase-like TDY Motif by Autophosphorylation and Cyclin-Dependent Protein Kinase-Activating Kinase Mol. Cell Biol. 2005 25 6047 6064 10.1128/MCB.25.14.6047-6064.2005 15988018
Chaya T. Omori Y. Kuwahara R. Furukawa T. ICK Is Essential for Cell Type-Specific Ciliogenesis and the Regulation of Ciliary Transport EMBO J. 2014 33 1227 1242 10.1002/embj.201488175
Moon H. Song J. Shin J.O. Lee H. Kim H.K. Eggenschwiller J.T. Bok J. Ko H.W. Intestinal Cell Kinase, a Protein Associated with Endocrine-Cerebro-Osteodysplasia Syndrome, Is a Key Regulator of Cilia Length and Hedgehog Signaling Proc. Natl. Acad. Sci. USA 2014 111 8541 8546 10.1073/pnas.1323161111 24853502
Wang E.J. Gailey C.D. Brautigan D.L. Fu Z. Functional Alterations in Ciliogenesis-Associated Kinase 1 (CILK1) That Result from Mutations Linked to Juvenile Myoclonic Epilepsy Cells 2020 9 694 10.3390/cells9030694
Lu I.L. Chen C. Tung C.Y. Chen H.H. Pan J.P. Chang C.H. Cheng J.S. Chen Y.A. Wang C.H. Huang C.W. et al. Identification of Genes Associated with Cortical Malformation Using a Transposon-Mediated Somatic Mutagenesis Screen in Mice Nat. Commun. 2018 9 2498 10.1038/s41467-018-04880-8
Sapio M.R. Vessaz M. Thomas P. Genton P. Fricker L.D. Salzmann A. Novel Carboxypeptidase A6 (CPA6) Mutations Identified in Patients with Juvenile Myoclonic and Generalized Epilepsy PLoS ONE 2015 10 123180 10.1371/journal.pone.0123180 25875328
Lopes M.W. Sapio M.R. Leal R.B. Fricker L.D. Knockdown of Carboxypeptidase A6 in Zebrafish Larvae Reduces Response to Seizure-Inducing Drugs and Causes Changes in the Level of MRNAs Encoding Signaling Molecules PLoS ONE 2016 11 152905 10.1371/journal.pone.0152905
Layouni S. Chouchane L. Malafosse A. Dogui M. Dimorphism of TAP-1 Gene in Caucasian with Juvenile Myoclonic Epilepsy and in Tunisian with Idiopathic Generalized Epilepsies Int. J. Immunogenet. 2010 37 117 123 10.1111/j.1744-313X.2010.00900.x
Goddard C.A. Butts D.A. Shatz C.J. Regulation of CNS Synapses by Neuronal MHC Class I Proc. Natl. Acad. Sci. USA 2007 104 6828 6833 10.1073/pnas.0702023104
Roshandel D. Sanders E.J. Shakeshaft A. Panjwani N. Lin F. Collingwood A. Hall A. Keenan K. Deneubourg C. Mirabella F. et al. SLCO5A1 and Synaptic Assembly Genes Contribute to Impulsivity in Juvenile Myoclonic Epilepsy NPJ Genom. Med. 2023 8 28 10.1038/s41525-023-00370-z
Holtkamp M. Kowski A.B. Merkle H. Janz D. Long-Term Outcome in Epilepsy with Grand Mal on Awakening: Forty Years of Follow-Up Ann. Neurol. 2014 75 298 302 10.1002/ana.24103 24395517
Rohracher A. Brigo F. Höfler J. Kalss G. Neuray C. Dobesberger J. Kuchukhidze G. Leitinger M. Trinka E. Perampanel for the Treatment of Primary Generalized Tonic-Clonic Seizures in Idiopathic Generalized Epilepsy Expert. Opin. Pharmacother. 2016 17 1403 1411 10.1080/14656566.2016.1195810 27267634
Bernhardt B.C. Rozen D.A. Worsley K.J. Evans A.C. Bernasconi N. Bernasconi A. Thalamo-Cortical Network Pathology in Idiopathic Generalized Epilepsy: Insights from MRI-Based Morphometric Correlation Analysis Neuroimage 2009 46 373 381 10.1016/j.neuroimage.2009.01.055
Li X. Wang Z. Chen Q. Wang X. Qing Z. Zhang W. Lu J. Wang J. Zhang X. Liu J. et al. Atrophy in the Left Amygdala Predicted Drug Responses in Idiopathic Generalized Epilepsy Patients with Tonic-Clonic Seizures Front. Neurosci. 2021 15 640016 10.3389/fnins.2021.640016 33867922
Abarrategui B. Parejo-Carbonell B. García García M.E. Di Capua D. García-Morales I. The Cognitive Phenotype of Idiopathic Generalized Epilepsy Epilepsy Behav. 2018 89 99 104 10.1016/j.yebeh.2018.10.007
Noda A. Hashizume R. Maihara T. Tomizawa Y. Ito Y. Inoue M. Kobayashi K. Asano Y. Sasa M. Serikawa T. NER Rat Strain: A New Type of Genetic Model in Epilepsy Research Epilepsia 1998 39 99 107 10.1111/j.1528-1157.1998.tb01281.x
Inoue M. Yamamoto A. Kaneko Y. Noda A. Naito H. Effects of Conventional Anticonvulsant Drugs on Generalized Tonic-Clonic Seizures in Noda Epileptic Rats Epilepsy Res. 2014 108 1158 1167 10.1016/j.eplepsyres.2014.05.004
Maihara T. Noda A. Yamazoe H. Voigt B. Kitada K. Serikawa T. Chromosomal Mapping of Genes for Epilepsy in NER: A Rat Strain with Tonic-Clonic Seizures Epilepsia 2000 41 941 949 10.1111/j.1528-1157.2000.tb00276.x
Kuramoto T. Voigt B. Nakanishi S. Kitada K. Nakamura T. Wakamatsu K. Yoshihara M. Suyama M. Uemura R. Tanaka M. et al. Identification of Candidate Genes for Generalized Tonic-Clonic Seizures in Noda Epileptic Rat Behav. Genet. 2017 47 609 619 10.1007/s10519-017-9870-2
Ohno Y. Shimizu S. Harada Y. Morishita M. Ishihara S. Kumafuji K. Sasa M. Serikawa T. Regional Expression of Fos-like Immunoreactivity Following Seizures in Noda Epileptic Rat (NER) Epilepsy Res. 2009 87 70 76 10.1016/j.eplepsyres.2009.07.012
Sejima H. Ito M. Kishi K. Noda A. Serikawa T. Regional Excitatory and Inhibitory Amino Acid Concentrations in Noda Epileptic Rat (NER) Brain Brain Dev. 1999 21 382 385 10.1016/S0387-7604(99)00037-6 10487471
Jinde S. Masui A. Morinobu S. Takahashi Y. Tsunashima K. Noda A. Yamada N. Kato N. Elevated Neuropeptide Y and Corticotropin-Releasing Factor in the Brain of a Novel Epileptic Mutant Rat: Noda Epileptic Rat Brain Res. 1999 833 286 290 10.1016/S0006-8993(99)01510-3 10375706
Jinde S. Masui A. Morinobu S. Noda A. Kato N. Differential Changes in Messenger RNA Expressions and Binding Sites of Neuropeptide Y Y1, Y2 and Y5 Receptors in the Hippocampus of an Epileptic Mutant Rat: Noda Epileptic Rat Neuroscience 2002 115 1035 1045 10.1016/S0306-4522(02)00545-6
Kiura Y. Hanaya R. Serikawa T. Kurisu K. Sakai N. Sasa M. Involvement of Ca2+ Channels in Abnormal Excitability of Hippocampal CA3 Pyramidal Cells in Noda Epileptic Rats J. Pharmacol. Sci. 2003 91 137 144 10.1254/jphs.91.137 12686757
Harada Y. Nagao Y. Shimizu S. Serikawa T. Terada R. Fujimoto M. Okuda A. Mukai T. Sasa M. Kurachi Y. et al. Expressional Analysis of Inwardly Rectifying Kir4.1 Channels in Noda Epileptic Rat (NER) Brain Res. 2013 1517 141 149 10.1016/j.brainres.2013.04.009
Mukai T. Kinboshi M. Nagao Y. Shimizu S. Ono A. Sakagami Y. Okuda A. Fujimoto M. Ito H. Ikeda A. et al. Antiepileptic Drugs Elevate Astrocytic Kir4.1 Expression in the Rat Limbic Region Front. Pharmacol. 2018 9 845 10.3389/fphar.2018.00845
Park J.C. Luebbers A. Dao M. Semeano A. Nguyen A.M. Papakonstantinou M.P. Broselid S. Yano H. Martemyanov K.A. Garcia-Marcos M. Fine-Tuning GPCR-Mediated Neuromodulation by Biasing Signaling through Different G Protein Subunits Mol. Cell 2023 83 2540 2558.e12 10.1016/j.molcel.2023.06.006
Lüttjohann A. van Luijtelaar G. The Role of Thalamic Nuclei in Genetic Generalized Epilepsies Epilepsy Res. 2022 182 106918 10.1016/j.eplepsyres.2022.106918
Guillery R.W. Feig S.L. Lozsádi D.A. Paying Attention to the Thalamic Reticular Nucleus Trends Neurosci. 1998 21 28 32 10.1016/S0166-2236(97)01157-0
Çavdar S. Onat F.Y. Çakmak Y.Ö. Yananli H.R. Gülçebi M. Aker R. The Pathways Connecting the Hippocampal Formation, the Thalamic Reuniens Nucleus and the Thalamic Reticular Nucleus in the Rat J. Anat. 2008 212 249 256 10.1111/j.1469-7580.2008.00858.x
Pantoja-Jiménez C.R. Magdaleno-Madrigal V.M. Almazán-Alvarado S. Fernández-Mas R. Anti-Epileptogenic Effect of High-Frequency Stimulation in the Thalamic Reticular Nucleus on PTZ-Induced Seizures Brain Stimul. 2014 7 587 594 10.1016/j.brs.2014.03.012 24794164
Chang W.J. Chang W.P. Shyu B.C. Suppression of Cortical Seizures by Optic Stimulation of the Reticular Thalamus in PV-MhChR2-YFP BAC Transgenic Mice Mol. Brain 2017 10 42 10.1186/s13041-017-0320-0
Clemente-Perez A. Makinson S.R. Higashikubo B. Brovarney S. Cho F.S. Urry A. Holden S.S. Wimer M. Dávid C. Fenno L.E. et al. Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms Cell Rep. 2017 19 2130 2142 10.1016/j.celrep.2017.05.044 28591583
Saalmann Y.B. Intralaminar and Medial Thalamic Influence on Cortical Synchrony, Information Transmission and Cognition Front. Syst. Neurosci. 2014 8 83 10.3389/fnsys.2014.00083
Mirski M.A. Ferrendelli J.A. Anterior Thalamic Mediation of Generalized Pentylenetetrazol Seizures Brain Res. 1986 399 212 223 10.1016/0006-8993(86)91511-8
Onat F.Y. van Luijtelaar G. Nehlig A. Snead O.C. The Involvement of Limbic Structures in Typical and Atypical Absence Epilepsy Epilepsy Res. 2013 103 111 123 10.1016/j.eplepsyres.2012.08.008 22989853
Peng J. Zhao L. The Origin and Structural Evolution of de Novo Genes in Drosophila Nat. Commun. 2024 15 810 10.1038/s41467-024-45028-1
Fischer F.P. Karge R.A. Weber Y.G. Koch H. Wolking S. Voigt A. Drosophila Melanogaster as a Versatile Model Organism to Study Genetic Epilepsies: An Overview Front. Mol. Neurosci. 2023 16 1116000 10.3389/fnmol.2023.1116000
Burg M.G. Wu C.F. Mechanical and Temperature Stressor-Induced Seizure-and-Paralysis Behaviors in Drosophila Bang-Sensitive Mutants J. Neurogenet. 2012 26 189 197 10.3109/01677063.2012.690011
Giachello C.N.G. Baines R.A. Inappropriate Neural Activity during a Sensitive Period in Embryogenesis Results in Persistent Seizure-like Behavior Curr. Biol. 2015 25 2964 2968 10.1016/j.cub.2015.09.040
Howe K. Clark M.D. Torroja C.F. Torrance J. Berthelot C. Muffato M. Collins J.E. Humphray S. McLaren K. Matthews L. et al. The Zebrafish Reference Genome Sequence and Its Relationship to the Human Genome Nature 2013 496 498 503 10.1038/nature12111 23594743
Hasani H. Sun J. Zhu S.I. Rong Q. Willomitzer F. Amor R. McConnell G. Cossairt O. Goodhill G.J. Whole-Brain Imaging of Freely-Moving Zebrafish Front. Neurosci. 2023 17 1127574 10.3389/fnins.2023.1127574 37139528
Burrows D.R.W. Samarut Liu J. Baraban S.C. Richardson M.P. Meyer M.P. Rosch R.E. Imaging Epilepsy in Larval Zebrafish Eur. J. Paediatr. Neurol. 2020 24 70 80 10.1016/j.ejpn.2020.01.006
D’Amora M. Galgani A. Marchese M. Tantussi F. Faraguna U. De Angelis F. Giorgi F.S. Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions Int. J. Mol. Sci. 2023 24 7702 10.3390/ijms24097702 37175408
Herculano-Houzel S. The Glia/Neuron Ratio: How It Varies Uniformly across Brain Structures and Species and What That Means for Brain Physiology and Evolution Glia 2014 62 1377 1391 10.1002/glia.22683
Kremer M.C. Jung C. Batelli S. Rubin G.M. Gaul U. The Glia of the Adult Drosophila Nervous System Glia 2017 65 606 638 10.1002/glia.23115
Kozol R.A. Abrams A.J. James D.M. Buglo E. Yan Q. Dallman J.E. Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish Front. Mol. Neurosci. 2016 9 55 10.3389/fnmol.2016.00055
Hinsch K. Zupanc G.K.H. Generation and Long-Term Persistence of New Neurons in the Adult Zebrafish Brain: A Quantitative Analysis Neuroscience 2007 146 679 696 10.1016/j.neuroscience.2007.01.071
Kalueff A.V. Stewart A.M. Gerlai R. Zebrafish as an Emerging Model for Studying Complex Brain Disorders Trends Pharmacol. Sci. 2014 35 63 75 10.1016/j.tips.2013.12.002
Depaulis A. David O. Charpier S. The Genetic Absence Epilepsy Rat from Strasbourg as a Model to Decipher the Neuronal and Network Mechanisms of Generalized Idiopathic Epilepsies J. Neurosci. Methods 2016 260 159 174 10.1016/j.jneumeth.2015.05.022
Sitnikova E. Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats) Biomedicines 2024 12 122 10.3390/biomedicines12010122 38255227
Charloteaux B. Zhong Q. Dreze M. Cusick M.E. Hill D.E. Vidal M. Protein-Protein Interactions and Networks: Forward and Reverse Edgetics Methods Mol. Biol. 2011 759 197 213 10.1007/978-1-61779-173-4_12 21863489
Vu V. Verster A.J. Schertzberg M. Chuluunbaatar T. Spensley M. Pajkic D. Hart G.T. Moffat J. Fraser A.G. Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes Cell 2015 162 391 402 10.1016/j.cell.2015.06.037 26186192
Sittig L.J. Carbonetto P. Engel K.A. Krauss K.S. Barrios-Camacho C.M. Palmer A.A. Genetic Background Limits Generalizability of Genotype-Phenotype Relationships Neuron 2016 91 1253 1259 10.1016/j.neuron.2016.08.013
Milutinovic S. Detich N. Szyf M. Valproate Induces Widespread Epigenetic Reprogramming Which Involves Demethylation of Specific Genes Carcinogenesis 2007 28 560 571 10.1093/carcin/bgl167
Silva C.G. Peyre E. Adhikari M.H. Tielens S. Tanco S. Van Damme P. Magno L. Krusy N. Agirman G. Magiera M.M. et al. Cell-Intrinsic Control of Interneuron Migration Drives Cortical Morphogenesis Cell 2018 172 1063 1078.e19 10.1016/j.cell.2018.01.031
Picardo M.A. Guigue P. Bonifazi P. Batista-Brito R. Allene C. Ribas A. Fishell G. Baude A. Cossart R. Pioneer GABA Cells Comprise a Subpopulation of Hub Neurons in the Developing Hippocampus Neuron 2011 71 695 709 10.1016/j.neuron.2011.06.018
Wang C.Z. Ma J. Xu Y.Q. Jiang S.N. Chen T.Q. Yuan Z.L. Mao X.Y. Zhang S.Q. Liu L.Y. Fu Y. et al. Early-Generated Interneurons Regulate Neuronal Circuit Formation during Early Postnatal Development Elife 2019 8 44649 10.7554/eLife.44649
Bitzenhofer S.H. Pöpplau J.A. Chini M. Marquardt A. Hanganu-Opatz I.L. A Transient Developmental Increase in Prefrontal Activity Alters Network Maturation and Causes Cognitive Dysfunction in Adult Mice Neuron 2021 109 1350 1364.e6 10.1016/j.neuron.2021.02.011
Favuzzi E. Huang S. Saldi G.A. Binan L. Ibrahim L.A. Fernández-Otero M. Cao Y. Zeine A. Sefah A. Zheng K. et al. GABA-Receptive Microglia Selectively Sculpt Developing Inhibitory Circuits Cell 2021 184 4048 4063.e32 10.1016/j.cell.2021.06.018
Poskanzer K.E. Yuste R. Astrocytes Regulate Cortical State Switching in Vivo Proc. Natl. Acad. Sci. USA 2016 113 E2675 E2684 10.1073/pnas.1520759113 27122314
Downes N. Mullins P. The Development of Myelin in the Brain of the Juvenile Rat Toxicol. Pathol. 2014 42 913 922 10.1177/0192623313503518
Williamson J.M. Lyons D.A. Myelin Dynamics Throughout Life: An Ever-Changing Landscape? Front. Cell Neurosci. 2018 12 424 10.3389/fncel.2018.00424
Lindhout F.W. Krienen F.M. Pollard K.S. Lancaster M.A. A Molecular and Cellular Perspective on Human Brain Evolution and Tempo Nature 2024 630 596 608 10.1038/s41586-024-07521-x 38898293
Degl’Innocenti E. Dell’Anno M.T. Human and Mouse Cortical Astrocytes: A Comparative View from Development to Morphological and Functional Characterization Front. Neuroanat. 2023 17 1130729 10.3389/fnana.2023.1130729
He Z. Han D. Efimova O. Guijarro P. Yu Q. Oleksiak A. Jiang S. Anokhin K. Velichkovsky B. Grünewald S. et al. Comprehensive Transcriptome Analysis of Neocortical Layers in Humans, Chimpanzees and Macaques Nat. Neurosci. 2017 20 886 895 10.1038/nn.4548
Ma S. Skarica M. Li Q. Xu C. Risgaard R.D. Tebbenkamp A.T.N. Mato-Blanco X. Kovner R. Krsnik Ž. de Martin X. et al. Molecular and Cellular Evolution of the Primate Dorsolateral Prefrontal Cortex Science 2022 377 ABO7257 10.1126/science.abo7257
Jorstad N.L. Song J.H.T. Exposito-Alonso D. Suresh H. Castro-Pacheco N. Krienen F.M. Yanny A.M. Close J. Gelfand E. Long B. et al. Comparative Transcriptomics Reveals Human-Specific Cortical Features Science 2023 382 ADE9516 10.1126/science.ade9516 37824638
Berto S. Mendizabal I. Usui N. Toriumi K. Chatterjee P. Douglas C. Tamminga C.A. Preuss T.M. Yi S.V. Konopka G. Accelerated Evolution of Oligodendrocytes in the Human Brain Proc. Natl. Acad. Sci. USA 2019 116 24334 24342 10.1073/pnas.1907982116
Xiang Y. Tanaka Y. Cakir B. Patterson B. Kim K.Y. Sun P. Kang Y.J. Zhong M. Liu X. Patra P. et al. HESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids Cell Stem Cell 2019 24 487 497.e7 10.1016/j.stem.2018.12.015
Kim J. Miura Y. Li M.-Y. Revah O. Selvaraj S. Birey F. Meng X. Thete M.V. Pavlov S.D. Andersen J. et al. Human Assembloids Reveal the Consequences of CACNA1G Gene Variants in the Thalamocortical Pathway Neuron 2024 112 4048 4059.e7 10.1016/j.neuron.2024.09.020 39419023
Kiral F.R. Cakir B. Tanaka Y. Kim J. Yang W.S. Wehbe F. Kang Y.J. Zhong M. Sancer G. Lee S.H. et al. Generation of Ventralized Human Thalamic Organoids with Thalamic Reticular Nucleus Cell Stem Cell 2023 30 677 688.e5 10.1016/j.stem.2023.03.007
Tringham E. Powell K.L. Cain S.M. Kuplast K. Mezeyova J. Weerapura M. Eduljee C. Jiang X. Smith P. Morrison J.L. et al. T-Type Calcium Channel Blockers That Attenuate Thalamic Burst Firing and Suppress Absence Seizures Sci. Transl. Med. 2012 4 3003120 10.1126/scitranslmed.3003120 22344687
Crunelli V. Leresche L. Block of Thalamic T-Type Ca2+ Channels by Ethosuximide Is Not the Whole Story Epilepsy Curr. 2002 2 53 56 10.1111/j.1535-7597.2002.00024.x
Shalomov B. Friesacher T. Yakubovich D. Combista J.C. Reddy H.P. Dabbah S. Bernsteiner H. Zangerl-Plessl E. Stary-Weinzinger A. Dascal N. Ethosuximide: Subunit- and Gβγ-Dependent Blocker and Reporter of Allosteric Changes in GIRK Channels Br. J. Pharmacol. 2025 182 1704 1718 10.1111/bph.17446 39814556
Glauser T.A. Holland K. O’Brien V.P. Keddache M. Martin L.J. Clark P.O. Cnaan A. Dlugos D. Hirtz D.G. Shinnar S. et al. Pharmacogenetics of Antiepileptic Drug Efficacy in Childhood Absence Epilepsy Ann. Neurol. 2017 81 444 453 10.1002/ana.24886
Lin C.H. Ho C.J. Chen S.Y. Lu Y.T. Tsai M.H. Review of Pharmacogenetics of Antiseizure Medications: Focusing on Genetic Variants of Mechanistic Targets Front. Pharmacol. 2024 15 1411487 10.3389/fphar.2024.1411487
Gouveia F.V. Warsi N.M. Suresh H. Matin R. Ibrahim G.M. Neurostimulation Treatments for Epilepsy: Deep Brain Stimulation, Responsive Neurostimulation and Vagus Nerve Stimulation Neurotherapeutics 2024 21 e00308 10.1016/j.neurot.2023.e00308
Velasco A.L. Velasco F. Jiménez F. Velasco M. Castro G. Carrillo-Ruiz J.D. Fanghänel G. Boleaga B. Neuromodulation of the Centromedian Thalamic Nuclei in the Treatment of Generalized Seizures and the Improvement of the Quality of Life in Patients with Lennox-Gastaut Syndrome Epilepsia 2006 47 1203 1212 10.1111/j.1528-1167.2006.00593.x
Sisterson N.D. Kokkinos V. Urban A. Li N. Richardson R.M. Responsive Neurostimulation of the Thalamus Improves Seizure Control in Idiopathic Generalised Epilepsy: Initial Case Series J. Neurol. Neurosurg. Psychiatry 2022 93 491 498 10.1136/jnnp-2021-327512
