Increased seizure susceptibility of the hippocampus compared with the neocortex of the immature mouse brain in vitro.
OBJECTIVE
The temporal lobe seems particularly susceptible to seizure activity. Mesial temporal lobe structures, including the hippocampus, have the lowest seizure thresholds in the brain. Conversely, thresholds in the frontal neocortex are significantly higher. The development of intact, isolated preparations of hippocampus and neocortex in vitro allows for study into mechanisms governing seizure threshold.


METHODS
Epileptiform discharges in isolated mouse neocortical blocks were compared with the contralateral intact hippocampus, isolated from the same brain, by using the low-Mg2+, 4 aminopyridine (4-AP), and low-Ca2+ in vitro seizure models. The pharmacology of low Mg(2+)-induced ictal-like events (ILEs) generated in the hippocampus and neocortex was then compared by using glutamatergic antagonists DL-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), and the Ca2+ channel antagonist, nifedipine.


RESULTS
Neocortical blocks generated both recurrent, spontaneous ILEs and interictal-like events under low-Mg2+ artificial CSF (aCSF) perfusion, distinct from those generated in the hippocampus. ILEs from the hippocampus displayed lower thresholds and longer durations as compared with isolated neocortical blocks. Similar results were obtained during 4-AP perfusion. Perfusion with low-Ca2+ ACSF did not produce stereotypical ILEs in the neocortical block, producing instead recurrent, slow depolarizations. Both ILEs and recurrent, slow depolarizations were produced in the hippocampus. Application of APV and nifedipine exacerbated low Mg(2+)-induced ILEs in the hippocampus but not the neocortex, indicating a distinct pharmacology for partial seizures of different brain regions.


CONCLUSIONS
The developing mouse hippocampus demonstrates increased ictogenesis compared with the developing neocortex in vitro, consistent with clinical observations and in vivo experimental models.
Abdelmalik
Peter A
PA
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Burnham
W McIntyre
WM
Carlen
Peter L
PL
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D006996:Hypocalcemia / Q000503:physiopathology; D066298:In Vitro Techniques; D008275:Magnesium Deficiency / Q000134:cerebrospinal fluid / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D009543:Nifedipine