Effects of Bicuculline Methiodide on Fast (>200 Hz) Electrical Oscillations in Rat Somatosensory Cortex

Abstract

Fast oscillatory activity (more than ∼200 Hz) has been attracting increasing attention regarding its possible role in both normal brain function and epileptogenesis. Yet, its underlying cellular mechanism remains poorly understood. Our prior investigation of the phenomenon in rat somatosensory cortex indicated that fast oscillations result from repetitive synaptic activation of cortical pyramidal cells originating from GABAergic interneurons ( Jones et al. 2000 ). To test this hypothesis, the effects of topical application of the γ-aminobutyric acid-A (GABAA) antagonist bicuculline methiodide (BMI) on fast oscillations were examined. At subconvulsive concentrations (∼10 μM), BMI application resulted in a pronounced enhancement of fast activity, in some trials doubling the number of oscillatory cycles evoked by whisker stimulation. The amplitude and frequency of fast activity were not affected by BMI in a statistically significant fashion. At higher concentrations, BMI application resulted in the emergence of recurring spontaneous slow-wave discharges resembling interictal spikes (IIS) and the eventual onset of seizure. High-pass filtering of the IIS revealed that a burst of fast oscillations accompanied the spontaneous discharge. This activity was present in both the pre- and the postictal regimes, in which its morphology and spatial distribution were largely indistinguishable. These data indicate that fast cortical oscillations do not reflect GABAergic postsynaptic currents. An alternate account consistent with results observed to date is that this activity may instead arise from population spiking in pyramidal cells, possibly mediated by electrotonic coupling in a manner analogous to that underlying 200-Hz ripple in the hippocampus. Additionally, fast oscillations occur within spontaneous epileptiform discharges. However, at least under the present experimental conditions, they do not appear to be a reliable predictor of seizure onset nor an indicator of the seizure focus.