NMDA receptor-dependent high-frequency network oscillations (100-300 Hz) in rat hippocampal slices

High-frequency oscillations (HFOs or ripples, >or=100 Hz) appear to be important expressions of cortical circuits, characterizing physiological and pathological functional states. Synaptic and non-synaptic mechanisms are involved in their generation. This study shows that spontaneous N-methyl-D-aspartate receptor (NMDAR) mediated potentials, recorded in dorsal and ventral hippocampal slices perfused with magnesium-free medium and antagonists of non-NMDARs and GABA receptors were associated with high-frequency oscillations (100-300 Hz), recorded in all hippocampal subregions. Both CA3 and CA1 regions displayed HFOs at the range of 180-300 Hz with oscillations in CA3 being significantly faster than in CA1 (232+/-22 Hz, n=64 slices versus 206+/-18 Hz, n=24, P<0.001). Moreover, in most of the slices (39/63) the CA1 network oscillated also at a lower frequency (121.8+/-2.45 Hz). Simultaneous recordings showed that activity was most often initiated in CA3 region; however, dentate gyrus and CA1 were potential sites of generation as well. The incidence of spontaneous events was significantly higher in ventral than in dorsal slices (20+/-1.6/min versus 5.4+/-0.3/min, P<0.001). The competitive and non-competitive NMDAR antagonists, d-AP5 (50 microM) and MK 801 (50 microM), respectively abolished spontaneous activity. The gap-junction blocker carbenoxolone significantly suppressed spontaneous activity in a concentration-dependent manner. These data indicate that synaptic transmission provided by solely NMDARs can sustain the generation of high-frequency network oscillations, which display distinct characteristics in CA3 and CA1 subregions.