Gamma oscillation underlies hyperthermia-induced epileptiform-like spikes in immature rat hippocampal slices

Background: Recently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41°C in an interface chamber induced epileptiform-like population spikes accompanied by a spreading depression (SD). This may serve as an in vitro model of febrile seizures. Results: In this study, we further investigate cellular mechanisms of hyperthermia-induced initial population spike activity. We hypothesized that GABA_A receptor-mediated 30-100 Hz γ oscillations underlie some aspects of the hyperthermic population spike activity. In 24 rat hippocampal slices, the hyperthermic population spike activity occurred at an average frequency of 45.9 ± 14.9 Hz (Mean ± SE, range = 21-79 Hz, n = 24), which does not differ significantly from the frequency of post-tetanic γ oscillations (47.1 ± 14.9 Hz, n = 34) in the same system. High intensity tetanic stimulation induces hippocampal neuronal discharges followed by a slow SD that has the magnitude and time course of the SD, which resembles hyperthermic responses. Both post-tetanic γ oscillations and hyperthermic population spike activity can be blocked completely by a specific GABA_A receptor blocker, bicuculline (5-20 μM). Bath-apply kynurenic acid (7 mM) blocks synaptic transmission, but fails to prevent hyperthermic population spikes, while intracellular diffusion of QX-314 (30 mM) abolishes spikes and produces a smooth depolarization in intracellular recording. Conclusion: These results suggest that the GABA_A receptor-governed γ oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.