An in vitro study on the role of excitatory amino-acid receptors in normal and epileptic neocortices

The putative neurotransmitters L-glutamate and L-aspartate can exert their excitatory action by activating the N-methyl-D-aspartate (NMDA) and non-NMDA receptors. The objective of this thesis is to investigate the physiological role of these excitatory amino-acid receptors in neocortical slices of normal rats and epileptic patients. My experiments in the rat neocortex indicate that excitatory synaptic transmission in normal artificial cerebrospinal fluid (ACSF) is primarily mediated by non-NMDA receptors, whereas the NMDA receptor is only activated when synaptic inhibition mediated by gamma-aminobutyric-acid-A receptors is reduced or blocked. Under such conditions, I found that the NMDA receptor participates in neuronal synchronization through polysynaptic circuits and contributes to the depolarization underlying the epileptiform discharge. In the epileptogenic human neocortex, I discovered that both NMDA and non-NMDA receptors are responsible for excitatory synaptic transmission in normal ACSF. Furthermore, their activation can lead to the appearance of epileptiform discharges. Together, the findings reported in this thesis suggest that the function of NMDA and non-NMDA receptors might be enhanced in the epileptogenic human neocortex, and lend further support to the hypothesis that excitatory amino acids are involved in epileptogenesis