title: Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations.
abstract: 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.
authors.affiliation: Institute of Cell Biology and Neurobiology.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stadler
authors.forename: Claudia
authors.initials: C
authors.lastname: Bierwirth
authors.forename: Luminita
authors.initials: L
authors.lastname: Stoenica
authors.forename: Arne
authors.initials: A
authors.lastname: Battefeld
authors.forename: Olivia
authors.initials: O
authors.lastname: Reetz
authors.forename: Eilhard
authors.initials: E
authors.lastname: Mix
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schuchmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Velmans
authors.forename: Karen
authors.initials: K
authors.lastname: Rosenberger
authors.forename: Anja U
authors.initials: AU
authors.lastname: Bräuer
authors.forename: Seija
authors.initials: S
authors.lastname: Lehnardt
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.forename: Matthias
authors.initials: M
authors.lastname: Budt
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Maarten H P
authors.initials: MH
authors.lastname: Kole
authors.forename: Ulf
authors.initials: U
authors.lastname: Strauss
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D003198:Computer Simulation; D016207:Cytokines / Q000502:physiology; D004569:Electroencephalography; D055724:Electrophysiological Phenomena / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000502:physiology*; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology*; D016899:Interferon-beta / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017471:Receptors, Interferon / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D016207:Cytokines; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007370:Interferon Type I; D015221:Potassium Channels; D017471:Receptors, Interferon; D016899:Interferon-beta