Elevation in Type I Interferons Inhibits HCN1 and Slows Cortical Neuronal Oscillations

摘要: Central nervous system (CNS) inflammation involves the generation of inducible cytokines such as interferons (IFNs) and alterations in brain activity, yet interplay both is not well understood. Here, we show that vivo elevation IFNs by viral infection reduced hyperpolarization-activated currents (Ih) cortical pyramidal neurons. In rodent slices directly exposed to type I IFNs, cyclic nucleotide (HCN)-gated channel subunit HCN1 was specifically affected. The effect required an intact receptor (IFNAR) signaling cascade. Consistent with Ih inhibition, hyperpolarized resting membrane potential, shifted resonance frequency, increased impedance. application IFN-β rat mouse cerebral cortex power higher frequencies electroencephalographic activity only presence HCN1. summary, these findings identify channels a novel neural target for providing possibility tune responses during complex event CNS inflammation.