INTERLEUKIN-1-BETA INHIBITS SYNAPTIC STRENGTH AND LONG-TERM POTENTIATION IN THE RAT CA1 HIPPOCAMPUS

Cytokines such as interleukin-1beta (IL-1beta) are released in the ner vous system following inflammation or infection. Recently, IL-1beta wa s shown to enhance synaptic inhibitory mechanisms. We therefore invest igated the effect of IL-1beta superfusion on long-term potentiation (L TP), the cellular model of memory and learning, evoked in the CA1 regi on by tetanic stimulation of the stratum radiatum in the rat hippocamp al slice. IL-1beta (150 pM-1.5 nM) superfused 10 min before tetanic st imulation significantly reduced LTP of the slope of the population exc itatory postsynaptic potential (pEPSP) and the population spike (PS) a mplitude in CA1 in a concentration-dependent manner. IL-1beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values befor e tetanus as well, although the PS returned to control values before t etanus. Heat-inactivated IL-1beta had no effect on pre-tetanus pEPSP o r PS values or the induction of LTP. These data demonstrate that IL-1b eta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dem entia.