Excitatory synaptic transmission mediated by NMDA and non-NMDA receptors in the superficial/middle layers of the epileptogenic human neocortex maintained in vitro.
Conventional intracellular recordings were made from regular-spiking cells located in layers II-IV to examine the involvement of excitatory amino acid receptors in synaptic transmission in epileptogenic human neocortical slices maintained in vitro. Extracellular stimuli that were below the threshold for generating action potentials evoked an excitatory postsynaptic potential (EPSP) with short latency to onset (0.8-4 ms). When suprathreshold stimuli were delivered, 95% of the neurons fired a single action potential. In 5% of the population, however, an all-or-none bursting discharge was observed. The EPSP and the bursting discharge were tested with the N-methyl-D-aspartate (NMDA) antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP, 5 microM) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 4 microM). In the presence of CNQX the peak amplitude of the EPSP was reduced by 85% and the bursting discharge was abolished completely. By contrast, CPP reduced the peak amplitude of the EPSP by 52%, attenuated the late phase of the bursting discharge and increased its threshold. These results indicate that excitatory amino acids function as excitatory transmitters in the human brain. While the involvement of non-NMDA receptors in the EPSP is in line with data from normal neocortical slices of other mammals, the participation of NMDA-mediated conductances to the EPSP appears peculiar to the epileptogenic human neocortex. This evidence, together with the contribution of NMDA and non-NMDA receptors to the all-or-none bursting discharge suggests that excitatory amino acid-mediated transmission might be modified in the epileptogenic human neocortex.
Department of Neurology, Montréal Neurological Institute, McGill University, Qué., Canada.
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology* / Q000601:surgery; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009924:Organ Culture Techniques; D010879:Piperazines / Q000494:pharmacology; D011612:Psychosurgery; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid