Syt1 and Syt2 redundantly support fast release at inhibitory synapses onto cerebellar Purkinje cells. A–D, Response to 10 Hz trains of optogenetic stimuli recorded in Purkinje neurons after virus-mediated expression of Cre-recombinase and oChIEF in the cerebellum. From top to bottom: blue trace represents 10 Hz light stimulus; black traces represent recorded IPSCs; black traces represent successive IPSCs in response to 10 Hz optical stimuli at higher time resolution (first three IPSCs only); red trace represents average IPSCs of 10 successive stimuli; histogram of event frequency for 100 ms following the light stimuli (average over 50 periods); histogram of spontaneous and asynchronous IPSC frequency before, during, and after the optogenetic stimulation train (red line indicates cumulative event frequency; blue line indicates average value for each 5 s interval). Light red trace in A represents the IPSCs in the presence of 10 μm bicuculline. D, Inset, Low-pass filtered (2 Hz) response to the 10 Hz optogenetic train (average of n = 10 traces). E, Individual and average values for IPSC amplitudes measured in all four genotype groups. F, The 20%–80% rise times (left) and IPSC decay time constants (right) for all four groups. In Syt2 KO synapses, the kinetic parameters could not be estimated because phasic evoked release events were absent (see D, bottom, red trace). G, Individual and average values for spontaneous IPSC frequency. H, Asynchronous IPSC frequency (left) and relative asynchronous release frequency (right). Number of recorded cells: wild-type synapses, n = 5; Syt1 KO synapses, n = 8; Syt2 KO synapses, n = 5; Syt1-Syt2 cDKO synapses, n = 5. Average data are presented as mean ± SEM. A significant difference was only observed in the comparisons involving the Syt1-Syt2 cDKO group (see asterisks), indicating that Syt1 and Syt2 act redundantly in inhibitory synapses on cerebellar Purkinje cells. *p < 0.05. **p < 0.01. ***p < 0.001.