Cross-talk between dopamine and noradrenaline modulates glutamatergic transmission in the deep cerebellar nuclei

Modulation of synaptic transmission in the deep cerebellar nuclei, a major output region of the cerebellum, is essential for regulating motor and non-motor functions by controlling information flow from the cerebellar cortex. In this study, we aimed to investigate the effects of dopamine (DA) and noradrenaline (NA) on glutamatergic synaptic transmission using cerebellar slices from both male and female Wistar rats. Stimulation-evoked excitatory postsynaptic currents (eEPSCs) were recorded from deep cerebellar nuclei neurons using whole-cell patch-clamp technique. Bath application of DA or NA decreased the eEPSC amplitude. Pharmacological analysis revealed presynaptic D2-like receptors (D2R) and α₂-adrenergic receptors (α₂-AdR) as mediators of the inhibitory effects induced by DA and NA, respectively. While DA decreased eEPSC amplitude in all tested synapses, the selective D2R agonist, quinpirole showed no effect in approximately 30% of synapses. By contrast, NA and α₂-AdR-selective agonists (clonidine and dexmedetomidine) inhibited synaptic transmission in all tested synapses. Notably, both DA and NA maintained their inhibitory effects even when their respective receptor antagonists (sulpiride and RS79948), were present. This observation suggests cross-receptor interactions: DA acted through α₂-AdRs, while NA operated via D2Rs. These findings reveal novel cross-talk of catecholamines within cerebellar networks, providing new insights into mechanisms underlying synaptic modulation.