Neuroscience Letters, 126 (1991) 167-171 0 1991 Elsevier Scientific Publishers Ireland Ltd. 0304-3940/91/S 03.50 ADONIS 030439409 100243P 167 NSL 07761 Iontophoretic application of NMDA produces different types of excitatory responses in developing human cortical and caudate neurons Carlos Cepeda’, Warwick Peacock2, Michael S. Levine’, and Nathaniel A. Buchwald’ ‘Mental Retardation Research Center and 2Division of Neurosurgery, University of Califotnia, Los Angeles, School of Medicine, Los Angeles, CA 90024 (U.S.A.) (Received 9 January 1991; Revised version received 11 February 1991; Accepted 15 ‘February 1991) Key wora!sis: Caudate; Development; Epilepsy; Human; Neocortex; NMDA The effects of iontophoretically applied N-methyl-D-aspartate (NMDA) were assessed in human neocortical and caudate neurons. NMDA depo- larized cell membranes, decreased input conductances and induced firing. The discharge patterns differed in the two areas studied. In neocortex, NMDA produced repetitive spikes or bursts. In caudate, it induced slow, rhythmic plateau depolarizations accompanied by an initial burst of action potentials, followed by low amplitude, long duration spikes. Afterhyperpolarizations were seen after each depolarization in the caudate. These varia- tions in patterns of excitation may relate to differences in local circuits intrinsic to each region, and/or to membrane conductances specific to each type of cell A number of reports have shown the feasibility of per- forming intracellular recordings in brain slices obtained from patients undergoing surgical treatment to alleviate epileptic seizures [ 1, 20, 23, 241. Recently, our group has conducted electrophysiological studies in an attempt to understand the cellular mechanisms of childhood cata- strophic epilepsy [27]. As part of these experiments, we have been investigating the effects of focal application of excitatory amino acids (EAAs) onto human neocortical and caudate neurons. The present experiment compares the electrophysiological effects of application of N- methyl-D-aspartate (NMDA) onto developing human neocortex and caudate neurons. NMDA is a potent EAA with selective agonist actions on a specific EAA receptor subtype (the NMDA recep- tor). The ionic mechanisms involved in excitation induced by activation of NMDA receptors is sui generis in that, in contrast to other EAA receptor subtypes, NMDA receptors are coupled to a voltage-dependent conductance. This dependency is created mainly by a blockade by Mg*+ of the NMDA receptor channel com- plex at hyperpolarized membrane potentials [19, 221. In animal studies, activation of NMDA receptors produces excitatory effects throughout the central nervous system Correspondence: C. Cepeda, Mental Retardation Research Center, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, U.S.A. [18]. However, the pattern of this excitation varies from region to region. In cat neocortex, in vitro, the initial res- ponse to NMDA application is a slow depolarization with stable repetitive firing followed by rhythmic depo- larization shifts with superimposed bursts of action potentials [ 111.In contrast, in the cat caudate nucleus, in vivo, iontophoretic application of NMDA induces pla- teau depolarizations with fast initial bursting followed by inactivation of Na+ spikes [13]. In rat neostriatum, in vitro, membrane oscillations and bursting activity oc- cur after bath application of NMDA [6]. In the present study we compared the effects of ionto- phoretically applied NMDA on human cortex and cau- date cells recorded in vitro. Our primary aim was to de- termine if there was a difference in the pattern of excita- tion displayed by cortical and caudate neurons. A second aim was to examine if local circuitry is sufficient to account for the generation of rhythmic bursting activ- ity and plateau depolarizations in the caudate nucleus or if this activity requires the presence of an intact extrinsic circuitry. Brain tissue samples were obtained from 10 patients suffering from intractable epilepsy (age range 3 months to 14 years). Hemispherectomies were performed to alle- viate symptoms of epilepsy. Neocortical samples were obtained from the temporal gyrus (6 cases), the posterior central gyrus (1 case), the precentral gyrus (1 case), the posterior superior frontal gyrus (1 case) and the occipital gyrus (1 case). In two cases (11 and 14 years of age), the