The varying extent of PTP within each group is shown in the cumulative histograms (Figure 2E). Significant differences between groups in the extent of PTP were apparent both in the cumulative histograms (Figure 2E) and in the summary plot of average potentiation (Figure 2F). In wild-type animals, the amplitude of enhancement ranged from 1.4-fold to 2.5-fold and averaged 1.81- ± 0.07-fold

(n = 17), which is similar to what has been described previously (Korogod et al., 2005, Korogod et al., 2007 and Lee et al., 2008). The extent of KPT-330 cell line PTP in slices from PKCα−/− animals (1.61- ± 0.06-fold, n = 13) was smaller than for wild-type animals (p < 0.01), and PTP was greatly reduced in PKCβ−/− (1.21- ± 0.02-fold, n = 15, p < 0.01) and PKCα−/−β−/− mice (1.16- ± 0.02-fold, n = 16, p < 0.01). These results suggest www.selleckchem.com/products/fg-4592.html an important role for calcium-dependent PKCs in PTP. To determine

whether deletion of PKCα/β selectively impairs PTP or whether other aspects of transmission are also altered, we examined the properties of basal synaptic transmission in slices from wild-type and double knockout animals. The amplitude and frequency of mEPSCs was the same in wild-types and PKC knockouts (see Figures S1A and S1B available online). We also measured the properties of use-dependent plasticity because changes in the initial probability of release alter the extent of use-dependent plasticity during high-frequency trains. These experiments were performed in the presence of kynurenate (1 mM) and cyclothiazide (0.1 mM) to reduce AMPA receptor saturation and desensitization, respectively, which can obscure changes in use-dependent plasticity. In Figure 3A, an example of excitatory postsynaptic currents (EPSCs) during 100 Hz train in a wild-type slice

is shown. The average normalized EPSC amplitudes (Figure 3B) were similar in wild-type (black) (n = 22) and PKCα−/−β−/− (purple) (n = 18) animals. There Florfenicol was no significant difference in the use-dependent plasticity in wild-type and in PKCα−/−β−/− mice (p = 0.24 for the second stimulus, p = 0.13 for the third stimulus, p = 0.08 for the average of the 31st to 40th stimuli) (Figure 3B). Synaptic currents evoked by stimulus trains can also be used to quantify the size of the vesicle pool that is readily released by a train (RRPtrain), as in Figure 3C. In this approach, the amplitudes of the EPSCs are measured and summated. In the plot of the cumulative EPSC, after approximately the first 10 EPSCs, RRPtrain is depleted, and the remaining steady-state EPSC is thought to reflect replenishment of RRPtrain. The cumulative EPSC (∑EPSC0) can then be determined by extrapolating back to the first EPSC in the train, as in Figure 3C. ∑EPSC0 is proportional to RRPtrain [RRPtrain = ∑EPSC0/(average mEPSC size)]. The fraction of vesicles (f0) within RRPtrain that is liberated by the first action potential in a train can then be determined (f0= EPSC0/∑EPSC0).