Premium
Immature Neurons and GABA Networks May Contribute to Epileptogenesis in Pediatric Cortical Dysplasia
Author(s) -
Cepeda Carlos,
André Véronique M.,
Wu Nanping,
Yamazaki Irene,
Uzgil Besim,
Vinters Harry V.,
Levine Michael S.,
Mathern Gary W.
Publication year - 2007
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2007.01293.x
Subject(s) - epileptogenesis , cortical dysplasia , neuroscience , excitatory postsynaptic potential , neurotransmission , gamma aminobutyric acid , bicuculline , gabaa receptor , electrophysiology , biology , glutamatergic , glutamate receptor , patch clamp , subplate , neocortex , epilepsy , cortex (anatomy) , inhibitory postsynaptic potential , receptor , biochemistry
Summary: Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has a number of similarities with immature cortex, such as reduced Mg 2+ sensitivity of N‐methyl‐D‐aspartate (NMDA) receptors and the persistence of subplate‐like neurons and undifferentiated cells. Because γ‐aminobutyric acid (GABA) is the main neurotransmitter in early cortical development, we hypothesized increased GABA receptor‐mediated synaptic function in CD tissue. Infrared videomicroscopy and whole‐cell patch clamp recordings were used to characterize the morphology and electrophysiological properties of immature and normal‐appearing neurons in slices from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy in children (0.2–14 years). In addition, we examined spontaneous and evoked synaptic activity, as well as responses to exogenous GABA application. We demonstrate both the presence of immature pyramidal neurons and networks in young CD tissue and the predominance of GABA synaptic activity. In addition, spontaneous GABA depolarizations frequently induced action potentials, supporting a potential excitatory role of GABA in CD. Evoked synaptic responses mediated by GABA were also prominent, and bath application of 4‐aminopyridine induced rhythmic depolarizations that were blocked by bicuculline. Finally, responses to exogenous application of GABA had depolarized reversal potentials in severe compared to mild and non‐CD cases. The present data support the hypothesis that CD shares features of immature cortex, with predominant and potentially excitatory GABA A receptor‐mediated neurotransmission. These results could partially explain the increased excitability of the cortical network in pediatric CD.