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 degrees 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 gamma 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 gamma 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 gamma oscillations and hyperthermic population spike activity can be blocked completely by a specific GABA(A) receptor blocker, bicuculline (5-20 microM). 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.


CONCLUSIONS
These results suggest that the GABA(A) receptor-governed gamma oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.
Wu
J
J
Division of Neurology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. jwu2@chw.edu
Javedan
S P
SP
Ellsworth
K
K
Smith
K
K
Fisher
R S
RS
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression; D004558:Electric Stimulation / Q000379:methods; D004827:Epilepsy / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005334:Fever / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; C012647:QX-314; D008012:Lidocaine; D007736:Kynurenic Acid