Interferon-α 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-α 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-α inhibited glutamate-mediated excitatory postsynaptic potentials (gEPSPs) and reversed or prevented long-term potentiation (LTP) induced by high-frequency tetanic stimulation. IFN-α reduced gEPSP amplitude far below its control value. Only a short-term potentiation (STP) was observed when either IFN-α or -2-amino-5-phosphonovalerato (APV; NMDA receptor antagonist) were present during tetanic stimulation. After this STP in presence of APV, IFN-α had no effect on gEPSPs. APV had no effect on LTP when applied after tetanic stimulation and did also not prevent IFN-α effect on LTP. Genistein (a tyrosine kinase inhibitor) or heat inactivation prevented IFN-α effects. IFN-α also decreased the depolarization induced by local application of glutamate but did not modify those induced by NMDA. Similarly, IFN-α reversed the potentiation (induced by tetanic stimulation) of glutamate-induced depolarizations. IFN-α did not affect long-term depression (LTD) induced by low-frequency tetanic stimulation. In conclusion, IFN-α-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-α unmasks LTD which is induced by the same high-frequency tetanic stimulation.