Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons

The neural transmission and plasticity can be differentially modulated by various elements of the immune system. Interferon-gamma (IFN-gamma) is a "pro-inflammatory" cytokine mainly produced by T lymphocytes, activates its corresponding receptor and plays important roles under both homeostatic and inflammatory conditions. However, the impact of IFN-gamma on the gamma-aminobutyric acid (GABA)-mediated currents in the hippocampus, a major brain region involved in the cognitive function, has not been investigated. Here we detected abundant expression of both IFN-gamma receptor subunit gene transcripts (Ifngrl and Ifngr2) in the rat hippocampus by quantitative PCR. In addition, we pre-incubated rat hippocampal slices with IFN-gamma (100 ng/ml) and recorded GABA-activated spontaneous and miniature postsynaptic inhibitory currents (sIPSCs and mIPSCs) and tonic currents in hippocampal CAl pyramidal neurons by the whole-cell patch-clamp method. The pre-incubation with IFN-gamma increased the frequency but not the mean amplitude, rise time or decay time of both sIPSCs and mIPSCs in hippocampal CAl pyramidal neurons, suggesting a presynaptic effect of IFN-gamma. Moreover, the GABA-activated tonic currents were enhanced by IFN-gamma. In conclusion, the potentiation of GABAergic currents in hippocampal neurons by IFN-gamma may contribute to the disturbed neuronal excitability and cognitive dysfunction during neuroinflammation.