Pacemaker GABA synaptic activity may contribute to network synchronization in pediatric cortical dysplasia

Carlos Cepeda; Jane Y. Chen; Joyce Y. Wu; Robin S. Fisher; Harry V. Vinters; Gary W. Mathern; Michael S. Levine

Neurobiology of Disease (Feb 2014)

Pacemaker GABA synaptic activity may contribute to network synchronization in pediatric cortical dysplasia

Carlos Cepeda,
Jane Y. Chen,
Joyce Y. Wu,
Robin S. Fisher,
Harry V. Vinters,
Gary W. Mathern,
Michael S. Levine

Affiliations

Carlos Cepeda: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA; Corresponding author at: Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience, Room 58-258, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA. Fax: +1 310 206 5060.
Jane Y. Chen: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA
Joyce Y. Wu: Division of Pediatric Neurology, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, USA
Robin S. Fisher: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA
Harry V. Vinters: Department of Neurology, Section of Neuropathology, David Geffen School of Medicine, University of California Los Angeles, USA
Gary W. Mathern: 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
Michael S. Levine: 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

Journal volume & issue: Vol. 62
pp. 208 – 217

Abstract

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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 (5–10 Hz) 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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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