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 properti es of CA1 hippocampal neurons using intracellular recordings. Superfusion o f this cytokine did not alter the resting membrane potential, cell input re sistance, action potentials, nor GABA-mediated fast synaptic potentials. IF N-alpha inhibited glutamate-mediated excitatory postsynaptic potentials (gE PSPs) and reversed or prevented long-term potentiation (LTP) induced by hig h-frequency tetanic stimulation. IFN-alpha reduced gEPSP amplitude far belo w its control value. Only a short-term potentiation (STP) was observed when either IFN-alpha or D-2-amino-5-phosphonovalerato (APV; NMDA receptor anta gonist) 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 a pplied after tetanic stimulation and did also not prevent IFN-alpha effect on LTP. Genistein (a tyrosine kinase inhibitor) or heat inactivation preven ted 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 stimula tion) of glutamate-induced depolarizations. IFN-alpha did not affect long-t erm depression (LTD) induced by low-frequency tetanic stimulation. In concl usion, IFN-alpha -induced inhibition of LTP is, at least in part, mediated by a postsynaptic effect, by tyrosine kinase activity, and by non-NMDA glut amate receptors. Inhibition of LTP by IFN-alpha unmasks LTD which is induce d by the same high-frequency tetanic stimulation. (C) 2000 Elsevier Science B.V. All rights reserved.