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

doi:10.1016/j.nbd.2013.10.001

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

Neurobiol Dis. 2014 Feb:62:208-17. doi: 10.1016/j.nbd.2013.10.001. Epub 2013 Oct 10.

Authors

Carlos Cepeda¹, Jane Y Chen², Joyce Y Wu³, Robin S Fisher², Harry V Vinters⁴, Gary W Mathern⁵, Michael S Levine⁶

Affiliations

¹ 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.
² Intellectual and Developmental Disabilities Research Center, Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, USA.
³ Division of Pediatric Neurology, Mattel Children's Hospital, David Geffen School of Medicine, University of California Los Angeles, USA.
⁴ Department of Neurology, Section of Neuropathology, David Geffen School of Medicine, University of California Los Angeles, USA.
⁵ 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.
⁶ 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.

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.

Keywords: Cortical dysplasia; Development; GABA; Pediatric epilepsy; Synaptic activity; Synchrony.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Child, Preschool
Cortical Synchronization / physiology
Epilepsy / physiopathology
Excitatory Postsynaptic Potentials
Humans
Infant
Inhibitory Postsynaptic Potentials
Malformations of Cortical Development / physiopathology*
Nerve Net / physiopathology
Pyramidal Cells / pathology
Pyramidal Cells / physiopathology*
Receptors, GABA-A / metabolism*
Synaptic Transmission*

Substances

Receptors, GABA-A

Abstract

Publication types

MeSH terms

Substances

Grants and funding