Interferon-alpha inhibits long-term potentiation and unmasks a long-term depression in the rat hippocampus.
Interferons (IFN) appear to have various neuromodulatory actions. Here, we characterized the actions of IFN-alpha on the electrophysiological properties of CA1 hippocampal neurons using intracellular recordings. Superfusion of this cytokine did not alter the resting membrane potential, cell input resistance, action potentials, nor GABA-mediated fast synaptic potentials. IFN-alpha inhibited glutamate-mediated excitatory postsynaptic potentials (gEPSPs) and reversed or prevented long-term potentiation (LTP) induced by high-frequency tetanic stimulation. IFN-alpha reduced gEPSP amplitude far below its control value. Only a short-term potentiation (STP) was observed when either IFN-alpha or D-2-amino-5-phosphonovalerato (APV; NMDA receptor antagonist) were present during tetanic stimulation. After this STP in presence of APV, IFN-alpha had no effect on gEPSPs. APV had no effect on LTP when applied after tetanic stimulation and did also not prevent IFN-alpha effect on LTP. Genistein (a tyrosine kinase inhibitor) or heat inactivation prevented IFN-alpha effects. IFN-alpha also decreased the depolarization induced by local application of glutamate but did not modify those induced by NMDA. Similarly, IFN-alpha reversed the potentiation (induced by tetanic stimulation) of glutamate-induced depolarizations. IFN-alpha did not affect long-term depression (LTD) induced by low-frequency tetanic stimulation. In conclusion, IFN-alpha-induced inhibition of LTP is, at least in part, mediated by a postsynaptic effect, by tyrosine kinase activity, and by non-NMDA glutamate receptors. Inhibition of LTP by IFN-alpha unmasks LTD which is induced by the same high-frequency tetanic stimulation.
Mendoza-Fernández
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Department of Anatomy and Cell Biology, Botterell Hall, Ninth Floor, Queen's University, Ontario K7L 3N6, Kingston, Canada.
Andrew
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Barajas-López
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019833:Genistein / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007155:Immunologic Factors; D016898:Interferon-alpha; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D019833:Genistein