Noradrenergic control of neuronal firing in cerebellar nuclei: modulation of GABA responses

The effects of noradrenaline (NA) on inhibitory responses to gamma aminobutyric acid (GABA) in neurones of the deep cerebellar nuclei were studied in vivo in rats, using extracellular single-unit recordings and microiontophoretic drug application. NA application altered GABA-evoked responses in 95 % of the neurones tested, but the effects differed between nuclei. Application of NA depressed GABA responses in the medial (MN) and posterior interpositus (PIN) nuclei, but enhanced GABA responses in the anterior interpositus nucleus (AIN). Comparable proportions of enhancing (57 %) and depressive (43 %) effects were found in the lateral nucleus (LN). The alpha2 noradrenergic receptor agonist clonidine mimicked the depressive effect of NA on GABA responses in MN and PIN and its enhancing effects in AIN and LN, while the alpha2 antagonist yohimbine partially blocked these effects. The beta-adrenergic agonist isoproterenol and antagonist timolol respectively induced and partially blocked enhancements of GABA responses in all nuclei except for LN, where isoproterenol had a weak depressive effect. It is concluded that NA modulates GABA responses by acting on both alpha2 and beta receptors. Activation of these receptors appears to be synergistic in the AIN and opposite in the remaining deep nuclei. These results support the hypothesis that the noradrenergic system participates in all the regulatory functions involving the cerebellum in a specific and differential manner, and suggest that any change in NA content, as commonly observed in ageing or stress, could influence cerebellar activity.