title: Pacemaker GABA synaptic activity may contribute to network synchronization in pediatric cortical dysplasia.
abstract: Spontaneous pacemaker γ-aminobutyric acid (GABA) receptor-mediated synaptic activity (PGA) occurs in a subset of tissue samples from pediatric epilepsy surgery patients. In the present study, based on single-cell electrophysiological recordings from 120 cases, we describe the etiologies, cell types, and primary electrophysiological features of PGA. Cells displaying PGA occurred more frequently in the areas of greatest anatomical abnormality in cases of focal cortical dysplasia (CD), often associated with hemimegalencephaly (HME), and only rarely in non-CD etiologies. PGA was characterized by rhythmic synaptic events (5-10Hz) and was observed in normal-like, dysmorphic cytomegalic, and immature pyramidal neurons. PGA was action potential-dependent, mediated by GABAA receptors, and unaffected by antagonism of glutamate receptors. We propose that PGA is a unique electrophysiological characteristic associated with CD and HME. It could represent an abnormal signal that may contribute to epileptogenesis in malformed postnatal cortex by facilitating pyramidal neuron synchrony.
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA. Electronic address: ccepeda@mednet.ucla.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Division of Pediatric Neurology, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: Robin S
authors.initials: RS
authors.lastname: Fisher
authors.affiliation: Department of Neurology, Section of Neuropathology, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA; Department of Neurosurgery, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, USA; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mathern
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003344:Cortical Synchronization / Q000502:physiology; D004827:Epilepsy / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials; D006801:Humans; D007223:Infant; D053444:Inhibitory Postsynaptic Potentials; D054220:Malformations of Cortical Development / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology; D017966:Pyramidal Cells / Q000473:pathology / Q000503:physiopathology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D011963:Receptors, GABA-A
keywords: Cortical dysplasia; Development; GABA; Pediatric epilepsy; Synaptic activity; Synchrony