Exogenous administration of the pro-inflammatory cytokine interleukin-1 (IL-1) inhibits long-term potentiation (LTP) in several regions of the hippocampus, both in vitro and in vivo (O’Connor & Coogan, 1999). Recent evidence suggests a role for endogenous IL-1 in LTP induction and/or maintenance (Schneider et al. 1998; Yirmiya et al. 2003). The aim of this study was to investigate the role of endogenous IL-1 in LTP using IL-1 receptor I knock out (IL-1RI KO) mice.
Field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 region of hippocampal slices prepared from IL-1RI KO mice or wild-type controls (C57 BL/6xSV129) (21-35 days old) humanely killed by cervical dislocation. Slices were incubated in normal aCSF at room temperature (21-24 °C) for at least 60 min in a holding chamber gassed with 95 % O2-5 % CO2. After this time individual slices were moved to a submerged chamber with the perfusing aCSF at 21-24, 29-30 or 34-36 °C. LTP was induced using a theta-burst stimulation (TBS) 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.). Data are expressed as means ± S.E.M. analysed 55-60 min after TBS. Statistical analysis within slices between pre- and post-TBS fEPSP slope values was done using Student’s paired t test. P < 0.05 was taken to be significant.
The magnitude of LTP at 21-24 °C did not differ between IL-1RI KO mice and wild-type (210 ± 30 % of control, n = 6, P < 0.05 and 189 ± 19 % of control, n = 5, P < 0.01, respectively). Similarly at 29-31 °C TBS resulted in statistically significant potentiation in hippocampal slices from wild-type mice and in slices from IL-1RI KO mice. Paired-pulse stimulation (inter-burst interval 40-800 ms) produced potentiation of fEPSP at all inter-burst intervals. There was no difference in the degree of potentiation obtained between wild-type and IL-1RI KO mice. TBS caused significant potentiation of fEPSP slope at 34-36 °C in slices from wild-type mice (203 ± 8 % of control, n = 4, P < 0.05) but not in slices from IL-1RI KO mice (134 ± 13 %, n = 4).
In conclusion, these results suggest that under certain circumstances endogenous IL-1, through the activation of IL-1RI, is involved in aspects of LTP and hence learning and memory.
This work was supported by MRC.