Activity-Dependent Release of Adenosine Contributes to Short-Term Depression at CA3-CA1 Synapses in Rat Hippocampus

Abstract

High-frequency stimulation results in a transient, presynaptically mediated decrease in synaptic efficacy called short-term depression (STD). Stimulation of Schaffer-collateral axons at 10 Hz for 5 s resulted in approximately 75% depression of excitatory postsynaptic current (EPSC) slope recorded from CA1 cells in rat organotypic slice cultures. An adenosine A1 receptor antagonist decreased the magnitude of STD elicited with 10-Hz stimulation by approximately 30%. The A1 receptor antagonist had no effect on STD elicited with 3-Hz stimulation. The activation of A1 receptors during 10-Hz stimulation was not due to the extracellular conversion of released ATP to adenosine, because block of 5′-ectonucleotidases did not significantly affect STD. The adenosine transport inhibitor dipyridamole did not reduce STD, indicating that adenosine was not released by facilitated transport. We conclude that 10-Hz, but not 3-Hz, stimulation causes the vesicular release of adenosine and the rapid (<3 s) activation of presynaptic inhibitory A1 receptors, which account for approximately 40% of homosynaptic EPSC depression.