Persistence of the neuromodulatory effects of adenosine on synaptic transmission after long-term potentiation and long-term depression

Abstract

Adenosine modulates long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. We tested whether induction of LTP or LTD might reciprocally modify the role of adenosine as an inhibitory modulator of synaptic transmission in the hippocampus. The experiments were performed on hippocampal slices of the rat. Two separate sets of the Schaffer pathway were alternately stimulated. Evoked field excitatory postsynaptic potentials (fEPSPs) were recorded extracellularly from CA1 stratum radiatum. Long-term potentiation (LTP) was induced by high-frequency stimulation and long-term depression (LTD) by low-frequency stimulation. The inhibitory effects of the adenosine analogue, 2-chloroadenosine (CADO, 0.1–5 μM), on the fEPSP slope were similar in both pathways (EC 50=0.72 (95% confidence intervals: 0.50–1.1) μM and EC 50=0.84 (0.55–1.3) μM, n=6). After induction of LTP in the test pathway, a second concentration–response curve was obtained. CADO was significantly less potent as compared to the first concentration–response curve, however the inhibitory effects of CADO were still similar in the potentiated pathway (EC 50=2.2 (1.6–3.1) μM) and in the control pathway (EC 50=2.1 (1.5–3.0) μM, n=6). The inhibitory effects of CADO (0.1–5 μM) were also not significantly different in the pathway where LTD was previously induced (EC 50=1.7 (1.5–2.0) μM), compared to the control non-depressed pathway (EC 50=1.7 (1.4–2.0) μM, n=6). In conclusion, the neuromodulatory action of adenosine seems to be maintained in the presence of substantial variations in long-term synaptic efficiency during LTP or LTD.