Glutamate, without GABA antagonists, induces synchronized discharges in intact hippocampus via NMDA receptors.
In rats under urethane anesthesia, iontophoresis of high amounts of glutamate (50-150 nA) in hippocampus caused repetitive field potentials. These synchronized discharges were best recorded in the proximal part of stratum radiatum as positive waves of 10-15 ms duration and of 0.5-5 mV amplitude. A tetrodotoxin-sensitive faster component of 2-5 ms duration was frequently superimposed on the peaks of the positive waves and was followed by a negative wave of 1-6 mV and 20-30 ms. Glutamate-evoked discharges were suppressed by iontophoresis of N-methyl-D-aspartate (NMDA) antagonists, MK-801, Mg2+ and ketamine and also by ketamine injection (i.v. 5-10 mg/kg). The population spikes evoked by fimbrial stimulation were not facilitated by glutamate and the synchronized discharges were suppressed for up to 300 ms following the stimulation, suggesting the presence of an efficient inhibition during glutamate-induced synchronized activity. Glutamate also had no effect on paired-pulse inhibition. No synchronized discharges were recorded with a second electrode separated more than 150 microns from the iontophoretic electrode, suggesting that the activity was local. These data demonstrate that high amounts of glutamate evoke synchronized discharges in hippocampus, possibly through activation of NMDA receptors. The model presented may be utilized to study the mechanisms of synchronization without disinhibition.
Dalkara
T
T
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Sofuoğlu
M
M
Onur
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D004558:Electric Stimulation; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D003986:Dibenzocycloheptenes; D005971:Glutamates; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D016291:Dizocilpine Maleate