Fig. 6: 5-HT4R activation boosts spontaneous synaptic activity in dissociated cultures while reduces excitatory CA3-CA1 transmission in CA1 pyramidal neurons.
a Representative recordings of mEPSCs in primary hippocampal neuronal cultures (DIV12) before (black trace) and 10 min after BIMU8 application (red trace) in neurons isolated from WT and 5-HT4R-deficient (KO) mice. b, c Summary of the mEPSC frequency (b) and the amplitude (c) before and 10 min after BIMU8 application in cultures from WT and KO mice (n = 6 cells for vehicle; n = 9 cells for BIMU8; n = 8 cells for BIMU8 in KO). **p < 0.01 (Wilcoxon paired test). d Time course of relative changes in average EPSC amplitude (left) recorded in CA1 pyramidal neurons in response to Schaffer collateral stimulation in control group (veh, n = 13 neurons) and slices treated with BIMU8 (10 μM, bath application; n = 10 neurons) or with 10 μM BIMU8 in the presence of a ROCK inhibitor, Y-27632 (50 μM, bath application; n = 8 neurons). Analysis performed for the first evoked EPSC in a low-frequency pulse train (5 times at 20 Hz, as shown on the top). Right, example traces of evoked EPSCs (first response) at different times after BIMU8 application alone or BIMU8 in the presence of Y-27632, as indicated. e. Summary of the relative changes in the EPSC amplitude (first response, as in d) at different times after BIMU8 application (left) and statistical comparison between control (veh) and BIMU8-treated groups at different time-points (right) (*p < 0.05, **p < 0.01, unpaired t-test). f Average paired-pulse ratio (PPR) for the first two EPSCs in CA1 pyramidal neurons evoked by Schaffer collateral stimulation (5 times at 20 Hz, as in d) in control (veh) and following BIMU8 application, either alone (red) or in the presence of a ROCK inhibitor Y-27632 (blue), and examples of evoked EPSCs recorded from the same cell at different times after BIMU8 application without or with Y-27632, as indicated. See also Supplementary Figs. 7 and 8. Data are presented as mean ± SEM.
