Dysfunction of Synaptic Inhibition in Epilepsy Associated with Focal Cortical Dysplasia

• DOI: 10.1523/jneurosci.2687-05.2005
• Publication Date: 2005-10-20T13:36:50Z
• Authors: Maria Elisa Calca...; Mercedes F. Paredes; Tarik Tihan; Nicholas M. Barbaro; Scott C. Baraban
• Keywords: Gamma-Aminobutyric Acid; Interneuron

Focal cortical dysplasia (FCD) is a common and important cause of medically intractable epilepsy. In patients with temporal lobe epilepsy in several animal models, compromised neuronal inhibition, mediated by GABA, contributes to seizure genesis. Although reduction GABAergic interneuron density has been reported FCD tissue samples, there little available information on the resulting physiological changes synaptic inhibition potential contribution these epileptogenesis dysplastic human brain. Using visualized whole-cell patch-clamp recordings from identified neurons slices obtained FCD, we demonstrate that GABAA-receptor-mediated substantially altered regions dysplasia. These alterations include significant IPSC frequency potentially compensatory decrease transporter-mediated GABA reuptake function; latter marked increase decay-time constant for evoked spontaneous IPSCs lack effect transport-inhibitor 1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride kinetics. Immunohistochemical staining revealed scattering interneurons across cortex striking reductions transporter expression. Together, results suggest profound GABA-mediated play an essential role process FCD.