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 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. CONCLUSION:These results suggest that the GABA(A) receptor-governed gamma oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.
journal_name
BMC Neuroscijournal_title
BMC neuroscienceauthors
Wu J,Javedan SP,Ellsworth K,Smith K,Fisher RSdoi
10.1186/1471-2202-2-18keywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
18issn
1471-2202journal_volume
2pub_type
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