Modeling pathogenesis and treatment response in childhood absence epilepsy

Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ‐aminobutyric acid (GABA) receptors and T‐type calcium channels implicated in the disorder. Previous studies of T‐type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T‐type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE.

[1]  Fiona E. N. LeBeau,et al.  Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts. , 2005, Journal of neurophysiology.

[2]  E. Perez-Reyes,et al.  Functional Characterization and Neuronal Modeling of the Effects of Childhood Absence Epilepsy Variants of CACNA1H, a T-Type Calcium Channel , 2005, The Journal of Neuroscience.

[3]  Jeffrey R Tenney,et al.  The Current State of Absence Epilepsy: Can We Have Your Attention? , 2013, Epilepsy currents.

[4]  Massimo Avoli,et al.  A brief history on the oscillating roles of thalamus and cortex in absence seizures , 2012, Epilepsia.

[5]  S. Vestermark,et al.  Clonazepam in the treatment of epilepsy. A controlled clinical trial in simple absences, bilateral massive epileptic myoclonus, and atonic seizures. , 1976, Archives of neurology.

[6]  Miles A Whittington,et al.  Combined Experimental/Simulation Studies of Cellular and Network Mechanisms of Epileptogenesis In Vitro and In Vivo , 2005, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[7]  Boyoung Lee,et al.  Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice , 2014, Proceedings of the National Academy of Sciences.

[8]  A. Destexhe.  Spike-and-Wave Oscillations Based on the Properties of GABAB Receptors , 1998, The Journal of Neuroscience.

[9]  A. Destexhe,et al.  Dendritic Low-Threshold Calcium Currents in Thalamic Relay Cells , 1998, The Journal of Neuroscience.

[10]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[11]  A. Depaulis,et al.  Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat. , 2000, Brain research. Molecular brain research.

[12]  D. Hirtz,et al.  Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy , 2017, Annals of neurology.

[13]  T. Sejnowski,et al.  A model of spindle rhythmicity in the isolated thalamic reticular nucleus. , 1994, Journal of neurophysiology.

[14]  Paul Tiesinga,et al.  Feeding the human brain model , 2015, Current Opinion in Neurobiology.

[15]  Caleb Davis,et al.  Exome Sequencing of Ion Channel Genes Reveals Complex Profiles Confounding Personal Risk Assessment in Epilepsy , 2011, Cell.

[16]  S. Charpier,et al.  Deep Layer Somatosensory Cortical Neurons Initiate Spike-and-Wave Discharges in a Genetic Model of Absence Seizures , 2007, The Journal of Neuroscience.

[17]  W. Lytton.  Computer modelling of epilepsy , 2008, Nature Reviews Neuroscience.

[18]  J. Noebels,et al.  Monogenic models of absence epilepsy: windows into the complex balance between inhibition and excitation in thalamocortical microcircuits. , 2014, Progress in brain research.

[19]  R. Dhamija,et al.  Review of Commercially Available Epilepsy Genetic Panels , 2016, Journal of Genetic Counseling.

[20]  D. Contreras,et al.  Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells. , 1998, Journal of neurophysiology.

[21]  M. Steriade,et al.  The reticular nucleus revisited: Intrinsic and network properties of a thalamic pacemaker , 2005, Progress in Neurobiology.

[22]  D. Hirtz,et al.  Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. , 2010, The New England journal of medicine.

[23]  O. Yalçin.  Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies , 2012, Seizure.

[24]  M. Weiergräber,et al.  Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. , 2001, Molecular pharmacology.

[25]  R. Rosch,et al.  Analysis of rare copy number variation in absence epilepsies , 2016, Neurology: Genetics.

[26]  M. de Curtis,et al.  Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  Alain Destexhe,et al.  LTS cells in cerebral cortex and their role in generating spike-and-wave oscillations , 2001, Neurocomputing.

[28]  Amos Bairoch,et al.  ICEPO: the ion channel electrophysiology ontology , 2016, Database J. Biol. Databases Curation.

[29]  T. Sejnowski,et al.  Computer model of ethosuximide's effect on a thalamic neuron , 1992, Annals of neurology.

[30]  W. Lennox.  The heredity of epilepsy as told by relatives and twins. , 1951, Journal of the American Medical Association.

[31]  M. Steriade.  Sleep oscillations in corticothalamic neuronal networks and their development into self-sustained paroxysmal activity. , 1993, Romanian journal of neurology and psychiatry = Revue roumaine de neurologie et psychiatrie.

[32]  Jennifer Vannest,et al.  Low‐ and high‐frequency oscillations reveal distinct absence seizure networks , 2014, Annals of neurology.

[33]  D Contreras,et al.  Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  P. Lory,et al.  Role of voltage-gated calcium channels in epilepsy , 2010, Pflügers Archiv - European Journal of Physiology.

[35]  K. Deisseroth,et al.  CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy , 2015, Genes & development.

[36]  W. Lytton,et al.  Computer model of antiepileptic effects mediated by alterations in GABAA‐mediated inhibition , 1998, Neuroreport.

[37]  Anna S. Bulanova,et al.  Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex , 2016, Neuroscience.