Long-term depression is not modulated by ATP receptors in the rat CA1 hippocampal region

ATP is an important extracellular messenger in the CNS. In the hippocampus, a brain structure relevant for learning and memory processes, it acts both as a modulator and as a mediator of synaptic transmission, with implications for synaptic plasticity phenomena. Recent evidence suggests that ATP modulates activity-dependent long-term potentiation (LTP) of Schaffer collateral-CA1 synapses. However, it remains unclear if ATP also modulates LTP counterpart's phenomenon, long-term depression (LTD), in the rat hippocampus. This study investigated the effect of ATP analogues on homosynaptic LTD, induced by low-frequency stimulation of the Schaffer collaterals (1 Hz; 900 pulses) in the CA1 region of young rat hippocampal slices. The metabolically stable ATP analogues β,γ-ImATP (20 μM), a P2 receptor agonist, and α,β-MeATP (20 μM), a preferential P2X1,3 receptor agonist, did not modify LTD (LTD values of 14.7 ± 0.5% and 14.1 ± 3% for aCSF controls and of 15.1 ± 4% and 19.0 ± 5.2% for β,γ-ImATP and α,β-MeATP, respectively). The ATP analogue β,γ-ImATP (20 μM) did not modify LTD also in the presence of the adenosine A1 receptor antagonist DPCPX (50 nM) (21.5 ± 4.2% for DPCPX only and of 23.8 ± 8.9% for DPCPX plus β,γ-ImATP). Finally, the preferential P2X1,3 receptor antagonist NF023 (10 μM) had also no effect on LTD (18.6 ± 5.2% for aCSF and of 18.7 ± 5.2% for NF023). The present results suggest that ATP does not modulate activity-dependent homosynaptic LTD in the rat CA1 hippocampal region by activating P2 receptors.