Figure 6: Shisa6 prolongs synaptic AMPAR currents and reduces synaptic depression.

(a) Example traces of mEPSC recordings from CA1 pyramidal cells of Shisa6 KO animals and WT littermates. (b,c) Superimposed spontaneous synaptic currents (b), and average synaptic currents (c) of Shisa6 KO animals and WT littermates. (d) Bar graphs (mean±s.e.m.) of Shisa6 KO and WT animals (n=19 cells per genotype, from four WT and four KO animals) represent rise time and decay time of mEPSCs, showing that both parameters are affected ex vivo. Amplitude was not significantly affected (16.21±0.52 versus 14.73±0.65 pA, P=0.085). (e) Superimposed example traces of whole-cell recording voltage clamped at −70 mV from CA1 pyramidal neurons of Shisa6 KO (blue) animals and WT littermates (black) in response to 50-Hz stimulation of synaptic inputs from Schaffer collateral fibres. (f–h) Pulse ratios of electrically evoked EPSCs from CA1 pyramidal neurons (at −70 mV) of Shisa6 KO (from five animals) animals and WT littermates (from six animals) at 2 (f), 20 (g) and 50 (h) Hz. At 20 Hz there was a trend for genotype effect (Gen, F(1,450)=3.52, P=0.067), and a significant effect of time (F(9,450)=17.81, P<0.001), as well as a genotype × time interaction (Gen-time, F(9,450)=3.91, P<0.001). The 50-Hz trains revealed a significant genotype effect (F(1,243)=7.33, P=0.012), time effect (F(9,243)=39.87, P<0.001) and a genotype × time interaction (F(9,243)=6.29, P<0.0001). Cell numbers used are indicated. *P<0.050 (Bonferroni post hoc test).