Research article

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

Jie Wu¹ , Sam P Javedan² , Kevin Ellsworth¹ , Kris Smith² and Robert S Fisher³

¹Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA

²Division of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix AZ 85013, USA

³Department of Neurology, Stanford University School of Medicine, 300 Pasteur Drive Stanford, CA 94305-5235, USA

author email corresponding author email

BMC Neuroscience 2001, 2:18doi:10.1186/1471-2202-2-18

Published:	28 November 2001

Abstract

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.