The Journal of Neurophysiology Vol. 87 No. 1 January 2002, pp. 634-639
Copyright ©2002 by the American Physiological Society

RAPID COMMUNICATION

Limbic Network Interactions Leading to Hyperexcitability in a Model of Temporal Lobe Epilepsy

 ¹Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada;  ²Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, 86077 Pozzilli (Isernia);  ³Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia, 41100 Modena; and  ⁴Dipartimento di Neuroscienze, Università degli Studi di Roma `Tor Vergata', 00173 Rome, Italy

D'Antuono, Margherita, Ruba Benini, Giuseppe Biagini, Giovanna D'Arcangelo, Michaela Barbarosie, Virginia Tancredi, and Massimo Avoli. Limbic Network Interactions Leading to Hyperexcitability in a Model of Temporal Lobe Epilepsy. J. Neurophysiol. 87: 634-639, 2002. In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4-aminopyridine (4AP, 50 µM) in hippocampus-EC slices from mice injected with pilocarpine 13-22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.