Abstracts

RATIONALE: Hyperthermia produces epileptiform activity in the rat hippocampal slice, with synchronous bursting of neurons, followed by spreading depressions (SDs). The depolarization early in an SD increases neuronal excitability, but the mechanisms of the bursting are unknown. We hypothesized that GABAA receptor-mediated gamma oscillations might underlie this bursting. Such gamma oscillations are believed to result from synchronization of inhibitory interneurons or from non-synaptic field effects.
METHODS: Experiments were performed on transverse hippocampal slices (450-500 [igrave]) from 23 Sprague-Dawley rats, ages 20 to 60 days. The artificial cerebrospinal fluid (CSF) comprised (mM): NaCl 117; KCl 5.4; NaHCO3 26; MgSO4 1.3; NaH2PO4 1.2; CaCl2 2.5; glucose 10. The pH was maintained at 7.4 by continuously bubbling 95% O2 plus 5% CO2 in an interface chamber. Slice chamber temperature was increased from baseline of 35 to 40 degrees centigrade over 15 minutes. Gamma oscillations were evoked either by a tetanic stimulation at 100 Hz for 200 ms or by hyperthermia.
RESULTS: Frequency of hyperthermic epileptiform activity was 45.9 [plusminus] 14.9 Hz(Mean [plusminus] SD, range 30 -79, n=24), similar to that of post-tetanic gamma oscillations (47.1 [plusminus] 14.9 Hz, n=34, p[gt]0.05). Conversely, tetanic stimulation in hippocampus produced gamma-band bursting, followed by a slow SD. Both post-tetanic gamma oscillations, and hyperthermic epileptiform activity could be blocked completely by the GABAA receptor blocker, bicuculline (5-20 mM). Bicuculline did not, however, block the SDs.
CONCLUSIONS: Hyperthermia activates GABAA receptor-mediated synchronization (gamma oscillations) in hippocampus, and these oscillations are correlated with epileptiform bursting.