title: A perturbation of multimodal GABA functions underlying the formation of focal cortical malformations: assessments by using animal models.
abstract: In order to study how the formation of focal cortical malformations is attributed to perturbation of developmentally multimodal γ-aminobutyric acid (GABA) functions, we made a focal cortical freeze-lesion on a rodent cerebral cortex at P0 (postnatal day 0). The microgyrus was formed at P7. GABA neurons were accumulated in the region surrounding necrosis at P4. Cortical plate cells born at E17.5 gathered, surrounding the GABA neurons, forming the cell dense portions in layer 2 of the microgyrus. Ambient GABA level was increased in the area corresponding to populated GABA neurons at P4. A KCC2 expression was downregulated, whereas an NKCC1 expression was upregulated in both the gathering GABA and cortical plate neurons, suggesting these cells had high intracellular Cl(-) concentration rendering GABA action depolarizing. GABAA receptor activation was involved in Ca(2+) oscillation in these gathering cells. In vivo blockade of GABAA receptor prevented the above characteristic pattern of cell accumulation and hence microgyrus formation. Thus, neonatal freeze-lesion causes characteristic accumulation of differential populations of neurons preceded by characteristic release of GABA at an early stage, which induces GABAA receptor-mediated depolarization and Ca(2+) oscillation. This paracrine/autocrine GABA may underlie the formation of neocortical malformations such as polymicrogyria.
authors: Department of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu, Japan. axfukuda@hama-med.ac.jp
authors: Atsuo
authors: A
authors: Fukuda
authors: Tianying
authors: T
authors: Wang
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D004195:Disease Models, Animal; D054220:Malformations of Cortical Development / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: GABA; chloride; cortex; migration; transporter