Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations

Cereb Cortex. 2014 Jan;24(1):199-210. doi: 10.1093/cercor/bhs305. Epub 2012 Oct 4.


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

Keywords: EEG; ion channels; neuroinflammation; viral infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Computer Simulation
  • Cytokines / physiology
  • Electroencephalography
  • Electrophysiological Phenomena / physiology
  • HEK293 Cells
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / physiology*
  • Immunohistochemistry
  • Interferon Type I / biosynthesis
  • Interferon Type I / physiology*
  • Interferon-beta / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Neocortex / cytology
  • Neocortex / metabolism
  • Neocortex / physiology
  • Nerve Net / cytology
  • Nerve Net / physiology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Potassium Channels / physiology*
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Receptors, Interferon / physiology
  • Signal Transduction / physiology
  • Transfection


  • Cytokines
  • Hcn1 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Interferon Type I
  • Potassium Channels
  • Receptors, Interferon
  • Interferon-beta