Kindling-induced epileptiform potentials in piriform cortex slices originate in the underlying endopiriform nucleus.
1. Previous studies in vivo and in vitro have shown that kindling from several locations in the limbic system induces the onset of epileptiform activity in the piriform (olfactory) cortex in the rat. In the present study we tested the hypothesis that kindled epileptiform events in piriform cortex are initiated in the underlying endopiriform nucleus. The experiments were performed in slices taken from rats that were previously kindled by conventional means. 2. Both stimulus-evoked and spontaneous interictal-like epileptiform events were observed in most slices from the anterior piriform cortex, but in few slices from the posterior piriform cortex. These events resembled those described in unanesthetized and urethan-anesthetized rats in previous studies. 3. Findings in support of the hypothesis were as follows. Epileptiform events in the endopiriform nucleus preceded those in the piriform cortex. Epileptiform events could occur in endopiriform nucleus alone, but were only observed in the piriform cortex following occurrence in the endopiriform nucleus. A buildup in population activity preceded the onset of all-or-none epileptiform events in the endopiriform nucleus. Epileptiform events could be triggered by local application of glutamate in the endopiriform nucleus and adjacent claustrum, but not from the piriform cortex. Finally, local application of Co2+ in the endopiriform nucleus, but not in the piriform cortex or elsewhere in the slices, blocked the occurrence of epileptiform events. 4. Additional experiments were performed to further characterize the generation process. 6,7-Dinitroquinoxaline-2,3-dione (DNQX) blocked epileptiform events and the preceding accelerating buildup in multiunit activity at a concentration below that required to block the monosynaptic excitatory postsynaptic potential (EPSP). This suggests that EPSPs mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors underlie epileptiform events in slices of piriform cortex, and that multisynaptic interactions within the endopiriform nucleus are required for generation of these epileptiform EPSPs. By contrast, block of N-methyl-D-aspartate (NMDA) receptors decreased the amplitude of epileptiform EPSPs but did not block their occurrence, indicating that NMDA receptors contribute to generation but are not required. When membrane potential was depolarized to increase driving force, fast inhibitory postsynaptic potentials were found to consistently accompany the buildup process and epileptiform EPSPs. This indicates that if initiation of epileptiform activity in the endopiriform nucleus results from a compromise in feedback inhibition, this compromise is partial rather than complete. 5. Epileptiform EPSPs in slices of piriform cortex from kindled rats displayed similarities in properties, locus of origin, and mechanism of generation to those previously studied in slices from normal rats in which epileptiform activity was induced by a brief period of bursting activity. These similarities suggest that study of bursting-induced epileptiform EPSPs may provide insight into certain aspects of kindling-induced epileptogenesis.
Hoffman
W H
WH
Department of Anatomy, University of Wisconsin, Madison 53706, USA.
Haberly
L B
LB
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009833:Olfactory Pathways / Q000033:anatomy & histology / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D003035:Cobalt; D018698:Glutamic Acid; C056723:FG 9041