Pro-inflammatory cytokine interleukin-1β (IL-1β) exerts a broad spectrum of neuromodulatory effects in the CNS in both physiological and pathological conditions. Recent investigations have demonstrated that IL-1β may disrupt processes of learning and memory, most likely through affecting synaptic transmission. Although the effects of IL-1β on basal synaptic transmission in the hippocampus remain controversial, there is more consensus with respect to the inhibition or at least reduction in the extent of long-term potentiation (LTP) exerted by this cytokine (O’Connor & Coogan, 1999). To explore the effect of IL-1β on basal synaptic transmission and to further investigate the effects of IL-1β on both high-frequency tetanus-induced and theta burst-induced LTP in the hippocampus was the object of this study.

Field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 region of hippocampal slices isolated from C56 BL6 mice (21-28 days old; animals were humanely killed according to UK legislation) in response to electrical stimulation of Schaffer collaterals. Slices were incubated in normal artificial cerebrospinal fluid (ACSF) for 60 min in a holding chamber gassed with 95 % O₂ and 5 % CO₂ prior to any test procedure. By applying electrical stimuli of increasing amplitude (0.5-5 V, 0.033 Hz) input-output and stimulation-response curves were generated. Two methods of LTP induction were used: a high frequency protocol (3 trains of 50 pulses at 100 Hz at twice stimulation intensity with an inter-train interval of 120 s) and a theta-burst protocol (5 trains of 15 bursts each consisting of 4 pulses at 100 Hz, with an inter-burst interval of 200 ms with the trains given at 0.1 Hz; Parent et al. 1998). Slices were either incubated with IL-1β (10 ng ml^-1) in a holding chamber for at least 75 min or IL-1β was added to a superfusing solution for a period of 30 min. Data are expressed as means ± S.E.M. Analysis among different groups was carried out using ANOVA; P < 0.05 was taken to indicate significance.

The regression line of input-output graphs and the fitting of the Boltzmann equation to stimulation-response graphs were used as indexes of basal synaptic strength. Hippocampal slices which had been incubated with IL-1β had a smaller slope of regression compared with slices which were incubated in normal ACSF (0.27 ± 0.05 vs. 0.7 ± 0.18 in control conditions; P < 0.05, n = 7). The effect of IL-1β was inhibited by a selective blocker of IL-1 receptors IL-1Ra (1000 ng ml^-1, n = 4). The maximum fEPSP slope was also reduced in IL-1β incubated slices (0.25 ± 0.06 vs. control value of 0.6 ± 0.13, n = 7). Perfusion of IL-1β for 30 min resulted in a small depression in fEPSP slope in hippocampal slices which were naive to IL-1β, the effect being completely blocked by IL-1Ra. Under the conditions of this study the high-frequency protocol produced a significant potentiation of the fEPSP (145 ± 15 % of control 30 min after the last train, n = 4, P < 0.05). This potentiation was reduced both by prior incubation of slices with IL-1β or by perfusion of slices with IL-1β 30 min before starting the high frequency protocol. In a similar manner IL-1β also reduced the extent of LTP induced by theta-burst protocol.

Thus we conclude that activation of IL-1β receptors may regulate synaptic plasticity in hippocampus.

This work was funded by the MRC.