Fig. 2
Noradrenaline (NA) decreased the amplitude of eEPSCs via α2-AdR activation. A: Inhibitory effect of NA on eEPSC amplitude. Left: Application of 10 μM NA markedly decreased the eEPSC amplitude (red trace). The traces shown are the averages of eight consecutive responses (black trace: baseline for 2 min; red trace: after 5–7 min of NA application). Right: Time course of changes in eEPSC amplitude induced by 10 μM NA in deep cerebellar nuclei neurons. B: Increase in PPR during NA application. PPRs were recorded before (Baseline) and 5–7 min after 10-μM NA application (NA). A significant increase in PPR was observed after NA application. Each column represents the mean ± SEM. C: Variance analysis of eEPSC in DCN neurons before and during the NA application. The ratio of CV–2 was plotted against the ratio of the mean eEPSC amplitude (n = 5). Both CV–2 and the mean eEPSC amplitude were determined by using 10 sweeps before and during the application of 10 μM NA. The filled circle represents means ± SEM. D: Concentration–response curves illustrating NA’s effects. Each data point represents the extent of eEPSC inhibition following a 5-min NA application at the corresponding concentration. Data are the least-mean square fit to a concentration–response curve with the Hill coefficient. Each point represents the mean ± SEM. The numbers adjacent to each point indicate the number of experiments. E and F: Pharmacological experiments revealed that the NA-induced inhibitory effect was mediated by α2-adrenergic receptor (α2-AdR) activation. The α2-AdR agonists clonidine (E) and dexmedetomidine (F) significantly decreased EPSC amplitude (left panels) and increased paired-pulse ratio (right panels) in deep cerebellar nuclei neurons. Conversely, the α1-adrenergic receptor agonist phenylephrine caused a slight decrease in eEPSC amplitude. However, PE application did not alter the paired-pulse ratio, suggesting that the underlying mechanism differs from the inhibitory effects associated with α2-AdR activation.
