Electrophysiological and morphological analyses of cortical neurons obtained from children with catastrophic epilepsy: Dopamine receptor modulation of glutamatergic responses

The present study examined the electrophysiological effects produced by act ivation of specific dopamine (DA) receptors and the distribution of DA rece ptor subtypes and glutamate receptor subunits [N-methyl-D-aspartate (NMDAR1 ) and GluR1] in cortical tissue samples obtained from children (ages 3 mont hs to 16 years) undergoing epilepsy surgery. DA receptor activation produce d differential effects depending on the receptor subtype that was activated . D1 receptor family agonists generally enhanced cortical excitability and favored the emergence of epileptogenic activity. In contrast, D2 receptor f amily agonists had more variable effects on cortical excitability and the e xpression of epileptiform discharges. Activation of D1 or D2 receptors decr eased the amplitude of non-NMDA-mediated excitatory postsynaptic potentials . In contrast, DA and D1 agonists increased the amplitude of NMDA-mediated potentials. Immunohistochemical analysis showed that the DA receptor subtyp es and glutamate receptor subunits examined were present in all cortical la yers and areas throughout development. Whole-cell voltage clamp recordings of pyramidal neurons visualized with differential interference contrast opt ics and infrared videomicroscopy indicated that these neurons displayed a p ersistent Na+ current, followed by an outward current. DA reduced the outwa rd current but had little effect on the persistent Na+ current. These resul ts suggest a dual role for DA's actions in the human cerebral cortex. Activ ation of D2 receptors or antagonism of D1 receptors may help control seizur es in children. Copyright (C) 1999 S. Karger AG, Basel.