Interneurons provide circuit-specific depolarization and hyperpolarization.

Perisoma-inhibiting interneurons (PIIs) control fundamental aspects of cortical network function by means of their GABAergic output synapses. However, whether they depolarize or hyperpolarize their target cells in the mature circuitry remains controversial. By using unitary field potential and gramicidin D perforated-patch recordings, we provide evidence that the postsynaptic effect of GABAergic synapses is fundamentally different in two regions of rat hippocampus. Signaling at PII output synapses is hyperpolarizing in CA1 principal cells (PCs) but depolarizing in dentate gyrus (DG) PCs. While the reversal potential of GABA(A) receptor-mediated currents is identical in both areas, ∼15 mV more negative resting potentials of DG compared with CA1 PCs underlie the opposing effects of perisomatic GABAergic transmission. Thus, the nature of PII output signaling is circuit-dependent and may therefore contribute differentially to information processing in the two brain areas.