Two-pool depletion model predicts frequency-dependent synaptic depression at cartwheel cell synapse. Two-pool depletion model predicts frequency-dependent synaptic depression at cartwheel cell synapse. A–C, Random (Poisson) evoked responses (red) centered at 5, 10, and 20 Hz are predicted by the two-pool depletion model (open circles). Each trace is from a different connection. C, Middle, Time course of the change in pool size during Poisson stimulation at 20 Hz. The low-Pr pool (black) has a faster recovery rate compared with the high-Pr pool (red); therefore, the depression is caused by the depletion of the high-Pr pool. D, Relative number of vesicles released from each pool during each stimuli. Low-Pr pool sustains the release after the synapse is depressed. E, Two-pool depletion model predicts the frequency-dependent depression evoked by spontaneous spiking. Solid circles represent data from Kuo and Trussell (2011). Gray dots represent predictions of the steady-state response of Poisson stimulation-evoked responses at various frequencies by the two-pool model. F, Two-pool depletion model shows that the low-Pr pool contributes most of the release during steady-state depression when the average firing frequency is >3 Hz. Hsin-Wei Lu, and Laurence O. Trussell J. Neurosci. 2016;36:3268-3280 ©2016 by Society for Neuroscience