title: Enhanced GABAergic network and receptor function in pediatric cortical dysplasia Type IIB compared with Tuberous Sclerosis Complex.
abstract: 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 GABA(A) 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.
authors: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA. ccepeda@mednet.ucla.edu
authors: Carlos
authors: C
authors: Cepeda
authors: Véronique M
authors: VM
authors: André
authors: Jason S
authors: JS
authors: Hauptman
authors: Irene
authors: I
authors: Yamazaki
authors: My N
authors: MN
authors: Huynh
authors: Julia W
authors: JW
authors: Chang
authors: Jane Y
authors: JY
authors: Chen
authors: Robin S
authors: RS
authors: Fisher
authors: Harry V
authors: HV
authors: Vinters
authors: Michael S
authors: MS
authors: Levine
authors: Gary W
authors: GW
authors: Mathern
mesh_terms: D000200:Action Potentials / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007395:Interneurons / Q000378:metabolism; D008297:Male; D054220:Malformations of Cortical Development / Q000378:metabolism* / Q000503:physiopathology; D018079:Receptors, GABA / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology; D014402:Tuberous Sclerosis / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018079:Receptors, GABA