Hippocampus-entorhinal cortex loop and seizure generation in the young rodent limbic system

Application of the convulsant 4-aminopyridine (4AP, 50 mu M) to adult mouse combined hippocampus-entorhinal cortex (EC) slices induces interictal and ictal discharges originating from CA3 and EC respectively. In this model of limbic seizures, ictal discharges disappear over time and are reestablishe d after Schaffer collateral cut, a procedure that blocks interictal propaga tion from CA3 to EC. Here we tested whether this form of network plasticity is operant in hippocampus-EC slices obtained from young (10-25 day-old) mi ce. In these experiments 4AP elicited interictal (duration = 100-250 ms; in terval = 0.7 +/- 0.2 s, mean +/- SD, n = 20) and ictal (duration = 267 +/- 37 s; interval = 390 +/- 37 s, n = 20) discharges in both CA3 and EC. Howev er, in young mouse slices the ictal events occurred throughout the experime nt, whereas Schaffer collateral cut abolished CA3-driven interictal dischar ges in EC without influencing ictal activity (n = 10). Perforant path lesio n prevented the spread of EC-driven ictal events to CA3, where interictal a nd short ictal discharges (duration = 32 +/- 11 s; interval = 92 +/- 9.7 s, n = 8) continued to occur. Hence, two independent forms of ictal activity were seen in CA3 and in EC after separation of these structures. In intact hippocampus-EC slices, ictal discharges were reduced by an N-methyl-D-aspar tate receptor antagonist (n = 10). Under these conditions, Schaffer collate ral cut abolished ictal activity in EC, not in CA3 (n = 6). Thus the young mouse hippocampus-EC loop has different properties as compared with adult t issue. These differences, which include the inability of hippocampal output s to control ictal discharge generation in EC and the ability of the loop t o sustain ictal activity, may contribute to the low-seizure threshold seen in young individuals.