Enhanced GABAergic network and receptor function in pediatric cortical dysplasia Type IIB compared with Tuberous Sclerosis Complex

Carlos Cepeda; Véronique M. André; Jason S. Hauptman; Irene Yamazaki; My N. Huynh; Julia W. Chang; Jane Y. Chen; Robin S. Fisher; Harry V. Vinters; Michael S. Levine; Gary W. Mathern

Neurobiology of Disease (Jan 2012)

Enhanced GABAergic network and receptor function in pediatric cortical dysplasia Type IIB compared with Tuberous Sclerosis Complex

Carlos Cepeda,
Véronique M. André,
Jason S. Hauptman,
Irene Yamazaki,
My N. Huynh,
Julia W. Chang,
Jane Y. Chen,
Robin S. Fisher,
Harry V. Vinters,
Michael S. Levine,
Gary W. Mathern

Affiliations

Carlos Cepeda: Intellectual and Developmental Disabilities Research Center, 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 90024, USA. Fax: +1 310 206 5060.
Véronique M. André: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, USA
Jason S. Hauptman: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, USA; Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, USA
Irene Yamazaki: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, USA
My N. Huynh: Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, USA
Julia W. Chang: Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, USA
Jane Y. Chen: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, USA
Robin S. Fisher: Intellectual and Developmental Disabilities Research Center, 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
Michael S. Levine: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, USA
Gary W. Mathern: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, USA; Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, USA

Journal volume & issue: Vol. 45, no. 1
pp. 310 – 321

Abstract

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Tuberous Sclerosis Complex (TSC) and cortical dysplasia Type IIB (CDIIB) share histopathologic features that suggest similar epileptogenic mechanisms. This study compared the morphological and electrophysiological properties of cortical cells in tissue from pediatric TSC (n=20) and CDIIB (n=20) patients using whole-cell patch clamp recordings and biocytin staining. Cell types were normal-appearing and dysmorphic–cytomegalic pyramidal neurons, interneurons, and giant/balloon cells, including intermediate neuronal–glial cells. In the cortical mantle, giant/balloon cells occurred more frequently in TSC than in CDIIB cases, whereas cytomegalic pyramidal neurons were found more frequently in CDIIB. Cell morphology and membrane properties were similar in TSC and CDIIB cases. Except for giant/balloon and intermediate cells, all neuronal cell types fired action potentials and displayed spontaneous postsynaptic currents. However, the frequency of spontaneous glutamatergic postsynaptic currents in normal pyramidal neurons and interneurons was significantly lower in CDIIB compared with TSC cases and the GABAergic activity was higher in all neuronal cell types in CDIIB. Further, acutely dissociated pyramidal neurons displayed higher sensitivity to exogenous application of GABA in CDIIB compared with TSC cases. These results indicate that, in spite of similar histopathologic features and basic cell membrane properties, TSC and CDIIB display differences in the topography of abnormal cells, excitatory and inhibitory synaptic network properties, and GABAA receptor sensitivity. These differences support the notion that the mechanisms of epileptogenesis could differ in patients with TSC and CDIIB. Consequently, pharmacologic therapies should take these findings into consideration.

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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