ROLE OF SYNAPTIC EXCITATION IN THE GENERATION OF BURSTING-INDUCED EPILEPTIFORM POTENTIALS IN THE ENDOPIRIFORM NUCLEUS AND PIRIFORM CORTEX

1. The mechanism of generation of epileptiform excitatory postsynaptic potentials (e-EPSPs) induced by bursting activity in vitro was examin ed in slices of piriform cortex. 2. Previous study reheated that e-EPS Ps in piriform cortex are generated in the subjacent endopiriform nucl eus. perhaps with a contribution from the claustrum and deep part of l ayer III of piriform cortex. A puzzling feature of these e-FPSPs was t heir abrupt origin at long latency with little sign of preceding abnor mal activity. 3. Systematic mapping revealed that within spatially res tricted regions of the endopiriform nucleus there is an irregular buil dup in extracellularly recorded multiunit activity and intracellularly recorded depolarization that precedes the onset of e-EPSPs. Analysis of latency revealed that these ''slow-onset'' e-EPSPs precede the more widely distributed ''abrupt-onset'' e-EPSPs, suggesting that they occ ur at sites of initiation. 4. The hypothesis was tested that the build up associated with slow-onset e-EPSPs is dependent on synaptically med iated excitation. According to this hypothesis, all-or-none e-EPSPs or iginate when mutually excitatory (positive feedback) interactions with in a population of cells in the endopiriform nucleus become self-regen erative. 5. Predictions from the regenerative positive feedback hypoth esis that were successfully verified include the presence of excitator y synaptic connections between cells in the endopiriform nucleus; the consistent prediction of a subsequent e-EPSP from the occurrence of th e accelerating buildup in population activity; the occurrence of inhib itory postsynaptic potentials (IPSPs) together with EPSPs during the b uildup period; and the blockage of the buildup and e-EPSP by a low con centration of a specific excitatory amino acid antagonist 6,7-dinitroq uinoxaline-2,3-dione (DNQX). 6. Blockage of e-EPSPs by a concentration of DNQX that was much less than that required to block monosynaptic E PSPs in the endopiriform nucleus indicates that synaptic reverberation is mediated by lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic aci d (AMPA) type excitatory amino acid receptors. 7. D-2-amino-5-phosphon ovaleric acid (D-APV) reduced the duration and amplitude of e-EPSPs bu t did not block their occurrence, indicating that N-methyl-D-aspartate (NMDA) receptors have a boosting effect on e-EPSPs but are not requir ed for their generation. This is in contrast to the induction of e-EPS Ps by bursting activity for which NMDA receptor activation is required . 8. Outside the region of initiation e-EPSPs propagated through the e ndopiriform nucleus at a velocity of 0.1 m/s. With increasing distance from initiation sites spiking associated with e-EPSPs became increasi ngly synchronous with a corresponding increase in the amplitude of ass ociated field potentials. 9. After pharmacological blockage of synapti c transmission, shock stimulation evoked a discrete volley in unmyelin ated axons whose peak propagated within the endopiriform nucleus at a velocity of 0.2 m/s. The propagation of e-EPSPs at a velocity less tha n that of the slowest-conducting axons suggests that propagation invol ves a regenerative process as previously modeled for the hippocampus.