Tetanic stimulation of area CA1 of hippocampal slices induces a slow depolarisation and sustained rhythmic firing. The relative roles of GABA_Aergic and metabotropic glutamatergic mechanisms in the depolarisation and of ephaptic interactions and IPSPs in the synchronisation of firing have been controversial (Bracci et al. 1999 vs. Whittington et al. 2001). In order to judge which mechanisms contribute under most physiological conditions we studied tetanus-induced oscillations in vivo.

Male Sprague-Dawley rats (280-350 g) were anaesthetised with 2.0 mg kg^-1 I.P. urethane and fixed in a stereotaxic frame. Bipolar stimulation electrodes were placed in the alveus and in stratum radiatum of hippocampus area CA1, 0.15 mm posterior to a 16-channel field potential recording probe. A 10 ml Hamilton syringe needle was placed in the ipsilateral ventricle, to apply drugs I.C.V. Rats were killed humanely at the end of the experiment.

The threshold stimulus intensity for evoking a fast λ oscillation (90 ± 4 Hz, mean ± S.E.M., n = 8) with a 10-pulse 100 Hz tetanus was 8 ± 1 V. Large-amplitude population spikes were induced with a small increase of stimulus intensity. At 1.5 X threshold intensity the tetanus evoked population spikes (maximum amplitude: 13 ± 1 mV, maximum field strength: 54 ± 6 V m^-1) starting at λ (71 ± 3 Hz), slowing down to β (11 ± 2 Hz) frequencies after 0.5 s, with small population spikes continuing at λ frequency (75 ± 2 Hz) between the large population spikes. Current source density analysis revealed that the discharge-related sink was confined to strata pyramidale/oriens and that the spontaneous discharge often started in stratum oriens. I.C.V. application of the metabotropic glutamate receptor antagonist MCPG (10 ml, 50 mM) reversibly reduced the amplitude and duration of the oscillation. The effects of MCPG were reversed by increasing stimulus intensity, or by co-application of the GABA_B receptor antagonist CGP 55845A (1 ml of 0.2 mM I.C.V.). In contrast the GABA_A receptor antagonist bicuculline (1 ml of 5 mM I.C.V.) completely blocked the oscillation at all intensities tested and in the presence of CGP 55845A.

These observations closely resemble our observations in interface recording chambers. The activity profile over the cell axis suggests strong ephaptic interactions due to ongoing high-frequency discharges in the non-tetanised dendrites. The pharmacological profile suggests that mGluR activation potentiates GABA release, necessary for a depolarising GABA response. These observations are consistent with those in vitro and indicate that depolarising GABA and strong ephaptic interactions play an important role in oscillations in vivo.

This work was supported by The Wellcome Trust and Epilepsy Research Foundation.

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