Changing the amount of synaptic utilization by APs. (A) Effect of pairing pre- and postsynaptic APs on the synaptic response to a 23-Hz train of presynaptic APs (experiment). The average response of 58 sweeps is shown before and 20 min after pairing. This effect is described in greater detail in (7). Pairing episodes were repeated 20 times every 30 sec. (B) Changing USE can mimic the effect of pairing. USE = 0.35 before pairing, USE = 0.67 after pairing. The rest of parameters are as in Fig. 1B. (C) Lowering extracellular calcium increases the rate of failures of the synaptic connection from 2.6 ± 2.17% (n = 19) to 21 ± 5.4% (n = 6) and slows the rate of synaptic depression. This effect has been recorded in 10 synaptic connections and is reversible (data not shown). Despite a marked decrease in the probability of release, the stationary EPSPs (last three EPSPs) are unaffected. Average responses (40 sweeps) to 30-Hz presynaptic APs are shown. (D) Two different synaptic connections selected to demonstrate that while the initial responses (low frequency) were markedly different, the stationary EPSPs (high frequency) were the same. The differences are due to different utilizations of efficacies (USE values) and not due to differences in absolute efficacies. Average responses (40 sweeps) to 23-Hz presynaptic APs are shown. (E) Redistribution of synaptic efficacy caused by acetylcholine (ACh). Bath application of 50 μM ACh reduced the initial (low frequency) responses (by 50–80%) and reduced the rate of depression for consecutive EPSPs, but had no effect on stationary EPSPs. This effect has been recorded in all 11 synaptic connections and reverses on washout of ACh (n = 9) or washing of a muscarinic receptor antagonist, atropine (n = 2). Average responses (30 sweeps) to 40-Hz presynaptic APs are shown. Concentrations as low as 10 μM were effective in reducing the low frequency EPSP by more than 10% (n = 3). Higher concentrations (above 200 μM) almost block transmission completely (n = 3). Maximum responses from A to E are normalized.