LAMINAR ORGANIZATION OF EPILEPTIFORM DISCHARGES IN THE RAT ENTORHINALCORTEX IN-VITRO

1. Interictal and ictal epileptiform discharges induced by 4-aminopyri dine (4AP, 50 mu M) were studied in the rat lateral entorhinal cortex with field potential and intracellular recordings in an in vitro slice preparation. Both types of discharge disappeared in layer II, but con tinued to occur in layers IV-VI after a knife cut separation was made at approximately 600 mu m from the pia (n = 4 slices). 2. Interictal d epolarizations recorded in layer IV-VI cells (amplitude, 29.4 +/- 8.6 mV; duration, 386 +/- 177.4 as, means +/- S.D.; n = 17) were capped by action potential bursts, while smaller interictal depolarizations in layer II cells (amplitude, 11.7 +/- 5.8 mV; duration, 192.6 +/- 47.9 m s; n = 10) were associated with single action potentials and were term inated by a hyperpolarization. Ictal discharges were initiated by an i nterictal discharge; they were characterized by a depolarization of 31 .5 +/- 6.2 mV (n = 12) in layer IV-VI and 11.6 +/- 3.5 mV (n = 7) in l ayer II neurones. 3. Slow, presumptive Ca2+-mediated spikes occurred i n layer II (n = 4) and IV-VI (n = 6) cells loaded with the Na+ channel blocker QX-314 (50 mM). These events were synchronized with populatio n spikes during interictal and ictal discharges, and were abolished by Ni2+ (1 mM, n = 4 cells) along with the 4AP-induced synchronous activ ity. 4. The N-methyl-D-aspartate (NMDA) receptor antagonist ,3-(2-carb oxypiperazine-4-yl)-propyl-1-phosphonate (CPP, 10 mu M) abolished icta l discharges and reduced interictal depolarizations in layer IV-VI neu rones (n = 4). The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxa line-2,3-dione (CNQX, 10 mu M) abolished both interictal and ictal act ivity (n = 4 cells). 5. These findings provide evidence for a role pla yed by NMDA-mediated mechanisms in the generation of epileptiform disc harges in the entorhinal cortex. Lack of an NMDA-mediated component al ong with presence of inhibition in layer II neurones results in attenu ation of epileptiform activity at this site. Moreover Ca2+-mediated sp ikes may contribute to the appearance of epileptiform discharges in th is model.