Epileptiform synchronization in the cingulate cortex.
OBJECTIVE
The anterior cingulate cortex (ACC)--which plays a role in pain, emotions and behavior--can generate epileptic seizures. To date, little is known on the neuronal mechanisms leading to epileptiform synchronization in this structure. Therefore, we investigated the role of excitatory and inhibitory synaptic transmission in epileptiform activity in this cortical area. In addition, since the ACC presents with a high density of opioid receptors, we studied the effect of opioid agonism on epileptiform synchronization in this brain region.


METHODS
We used field and intracellular recordings in conjunction with pharmacological manipulations to characterize the epileptiform activity generated by the rat ACC in a brain slice preparation.


RESULTS
Bath-application of the convulsant 4-aminopyridine (4AP, 50 microM) induced both brief and prolonged periods of epileptiform synchronization resembling interictal- and ictal-like discharges, respectively. Interictal events could occur more frequently before the onset of ictal activity that was contributed by N-methyl-D-aspartate (NMDA) receptors. Mu-opioid receptor activation abolished 4AP-induced ictal events and markedly reduced the occurrence of the pharmacologically isolated GABAergic synchronous potentials. Ictal discharges were replaced by interictal events during GABAergic antagonism; this GABA-independent activity was influenced by subsequent mu-opioid agonist application.


CONCLUSIONS
Our results indicate that both glutamatergic and GABAergic signaling contribute to epileptiform synchronization leading to the generation of electrographic ictal events in the ACC. In addition, mu-opioid receptors appear to modulate both excitatory and inhibitory mechanisms, thus influencing epileptiform synchronization in the ACC.
Panuccio
Gabriella
G
Department of Neurology, Montreal Neurological Institute , McGill University, Montreal, QC, Canada.
Curia
Giulia
G
Colosimo
Alfredo
A
Cruccu
Giorgio
G
Avoli
Massimo
M
D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003344:Cortical Synchronization; D004569:Electroencephalography / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004828:Epilepsies, Partial / Q000139:chemically induced / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015761:4-Aminopyridine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000927:Anticonvulsants; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018756:GABA Antagonists; D010879:Piperazines; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid