The Journal of Neurophysiology Vol. 84 No. 3 September 2000, pp. 1355-1360
Copyright ©2000 by the American Physiological Society

Hyperthermic Spreading Depressions in the Immature Rat Hippocampal Slice

 ¹Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix 85013-4496; and  ²Neurology, University of Arizona, Tucson, Arizona 85721

Wu, Jie and Robert S. Fisher. Hyperthermic Spreading Depressions in the Immature Rat Hippocampal Slice. J. Neurophysiol. 84: 1355-1360, 2000. Febrile seizures are the most common seizure type in children (6 mo to 5 yr). The pathophysiology of febrile seizures is unknown. Current genetic studies show that some febrile seizures result from channelopathies. We have performed electrophysiological experiments in in vitro hippocampal slices to test a novel hypothesis that a disordered regulation of ionic homeostasis underlies the genesis of febrile seizures. In transverse hippocampal CA1 slices from 104 rats, temperature increase from 34° to 40°C produced a series of spreading depressions (SDs), called hyperthermic SDs. The hyperthermic SDs were age-dependent, occurring in only 1/17 8-16 day-old animals, 44/49 17-60 day-old animals, and 11/20 rats older than than 60 days. The hyperthermic SDs usually occurred on the rising phase of the temperature. The mean temperature to trigger a first hyperthermic SD was 38.8 ± 1.3°C (mean ± SD, n = 44). The hyperthermic SDs induced a reversible loss of evoked synaptic potentials and a dramatic decrease of input resistance. Neuronal and field epileptiform bursting occurred in the early phases of the hyperthermic SD. During hyperthermic SDs, pyramidal cell membrane potential depolarized by 38.3 ± 4.9 mV (n = 20), extracellular field shifted negative 18.5 ± 3.9 mV (n = 44), and extracellular K⁺ rose reversibly to 43.8 ± 10.9 mM (n = 6). Similar SDs could be evoked by ouabain or transient hypoxia with normal temperature. Tetrodotoxin could block initial epileptiform bursting, without blocking SDs. Hyperthermia-induced SDs should be investigated as possible contributing factors to febrile seizures.