Beta-adrenergic enhancement of inhibitory synaptic activity in rat cerebellar stellate and Purkinje cells.

1. Using the tight-seal whole-cell recording technique, we studied the effects of noradrenaline (NA) on the spontaneous inhibitory synaptic currents (IPSCs) of stellate and Purkinje cells in rat cerebellar slices. 2. In both types of cells, NA (10 microM) induced a marked increase in the frequency of the IPSCs. This effect was observed both in the absence and in the presence of TTX in the saline bathing the cerebellar slices. 3. The NA-induced increase in frequency of IPSCs and miniature IPSCs (mIPSCs) in the two cell types was mimicked by bath applications of isoprenaline (10 microM) and of the adenylyl cyclase activator forskolin (20 microM). Neither phenylephrine nor clonidine changed the frequency of IPSCs in stellate or Purkinje cells. 4. In stellate cells, the beta-agonists and forskolin had variable effects on the amplitudes of both IPSCs and mIPSCs. None of these compounds altered the amplitude of mIPSCs in Purkinje cells. 5. The responses to local applications of GABA to Purkinje cells were unchanged by bath applications of beta-adrenergic agonists or forskolin. A decrease in the response to GABA after treatment with these agents was observed in half the stellate cells examined. 6. We conclude that the major effect of NA on stellate and Purkinje cells is an increase in the frequency of occurrence of spontaneous inhibitory synaptic currents. This action is exerted through the activation of beta-adrenergic receptors and is probably mediated by an intracellular mechanism involving cAMP. The beta-adrenergic modulation of IPSC frequency takes place at the presynaptic level and may involve a change in the process of transmitter release.