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

High-frequency oscillations (HFOs or ripples, ≥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 μM) and MK 801 (50 μM), 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.