7mV ± 2.8mV; n = 12), indicating a depolarizing action of GABA. We also found that high-frequency

stimulation of HS cells evoked action potentials in their target cells (n = 5 SHFs; Figure S3E2b). LY2157299 in vitro These results show that HS cell firing can entrain their target neurons, probably via the depolarizing action of GABA. Our next proposal was a recruitment of interneurons by the HS cells. If HS firing entrained these interneurons, then two requirements should be met: (1) high-frequency GABA currents should occur in interneurons before GFOs, because HS cells, which contact interneurons, always fire before GFOs at high frequency; and (2) high-frequency GABA currents should occur in turn after GFO onset in pyramidal cells, because interneurons, which contact pyramidal cells, fire at high frequency during GFOs. Whole-cell recordings of interneurons revealed that large synaptic GABA currents with a high-frequency component always preceded field GFOs (mean: 183 ms; range: 40–450 ms; n = 17; Figure 3C). Because pyramidal cell-projecting interneurons fire at high frequency during GFOs (Figure 2A), pyramidal cells received a high-frequency barrage of GABAergic inputs during GFOs (Figure 3C). The frequency

of GABAergic inputs in pyramidal cells (88 ± 17 Hz; n = 9) was similar to the firing frequency of interneurons and to the field GFOs. In contrast, the fast oscillatory component within the glutamatergic drive occurred after the initiation of GFOs in all recorded interneurons (n = 17) and pyramidal cells (n = 9) and had a lower magnitude than GABA currents (Figures 3C2 and 3C3). The analysis BKM120 order of synaptic activity thus reveals a sequential recruitment of the different actors in the network: at first, a population of GABA neurons

(interneuron-specific GABA neurons), which contact interneurons, but not pyramidal cells, starts to fire before GFOs. This is consistent with the HS cells’ specific targeting and firing pattern. This suggests that GABAergic currents provide the main synaptic drive onto interneurons. In turn, these interneurons fire during GFOs. Pyramidal cells also fire during GFOs, although to a lesser extent. If HS cells play a leading role and are necessary for GFO emergence, preventing their Mannose-binding protein-associated serine protease firing should abolish GFOs. To test causality, we used GIN (GFP-expressing inhibitory neurons) mice in which green fluorescent protein (GFP) is expressed via the GAD67 promoter only in somatostatin-containing neurons, including HS cells (Oliva et al., 2000). At P6, most GFP-containing neurons recorded in CA1 stratum oriens were identified post hoc as HS cells (72%; n = 18/25). The 28% that remained were all identified as O-LM cells (n = 7/25). Recordings of GFP-negative interneurons revealed the presence of O-LM cells, but not HS cells (n = 14 O-LM cells and 14 other types of interneurons; data not shown).