Hippocampus-entorhinal cortex loop and seizure generation in the young rodent limbic system.
Application of the convulsant 4-aminopyridine (4AP, 50 microM) 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 reestablished after Schaffer collateral cut, a procedure that blocks interictal propagation 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) mice. In these experiments 4AP elicited interictal (duration = 100-250 ms; interval = 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. However, in young mouse slices the ictal events occurred throughout the experiment, whereas Schaffer collateral cut abolished CA3-driven interictal discharges in EC without influencing ictal activity (n = 10). Perforant path lesion prevented the spread of EC-driven ictal events to CA3, where interictal and 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-aspartate receptor antagonist (n = 10). Under these conditions, Schaffer collateral 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 tissue. These differences, which include the inability of hippocampal outputs to control ictal discharge generation in EC and the ability of the loop to sustain ictal activity, may contribute to the low-seizure threshold seen in young individuals.
Calcagnotto
M E
ME
Montreal Neurological Institute, Department of Neurology and Neurosurgery and Department of Physiology, McGill University, Montreal, Quebec H3A 2B4, Canada.
Barbarosie
M
M
Avoli
M
M
D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D019580:Perforant Pathway / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C104291:3-(2-carboxypiperazine-4-yl)propyl-1-phosphate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015761:4-Aminopyridine