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Pacemaker GABA synaptic activity may contribute to network synchronization in pediatric cortical dysplasia.

  • Author(s): Cepeda, Carlos
  • Chen, Jane Y
  • Wu, Joyce Y
  • Fisher, Robin S
  • Vinters, Harry V
  • Mathern, Gary W
  • Levine, Michael S
  • et al.
Abstract

Spontaneous pacemaker γ-aminobutyric acid (GABA) receptor-mediated synaptic activity (PGA) occurs in a subset of tissue samples from pediatric epilepsy surgery patients. In the present study, based on single-cell electrophysiological recordings from 120 cases, we describe the etiologies, cell types, and primary electrophysiological features of PGA. Cells displaying PGA occurred more frequently in the areas of greatest anatomical abnormality in cases of focal cortical dysplasia (CD), often associated with hemimegalencephaly (HME), and only rarely in non-CD etiologies. PGA was characterized by rhythmic synaptic events (5-10Hz) and was observed in normal-like, dysmorphic cytomegalic, and immature pyramidal neurons. PGA was action potential-dependent, mediated by GABAA receptors, and unaffected by antagonism of glutamate receptors. We propose that PGA is a unique electrophysiological characteristic associated with CD and HME. It could represent an abnormal signal that may contribute to epileptogenesis in malformed postnatal cortex by facilitating pyramidal neuron synchrony.

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