A-C, averaged responses to single presynaptic spikes and spike pairs with different interspike intervals are superimposed, with thin and thick traces alternating. A, averaged responses to all spike pairs at the intervals illustrated. Second EPSPs are on average depressed, recovering with longer intervals. Representative presynaptic spike pairs are shown above (baselines shifted for clarity, all holding potentials in this example similar). B, at short intervals, second EPSPs following first spike failures are depressed relative to the average first EPSP (grey trace). C, second EPSPs are similarly depressed (relative to average first EPSPs) at 0.33 Hz (B) and at 1 Hz (C), when the readily releasible transmitter pool is reversibly exhausted, or ‘fatigued’. Release-independent and release-dependent depression, with facilitation and fatigue would explain these data.