Locus coeruleus stimulation potentiates local inhibitory processes in rat cerebellum

We previously reported that a low threshold action of norepinephrine (NE) on the cerebellar circuitry is expressed as an amplification of the inhibitory action of gamma aminobutyric acid (GABA) on Purkinje cell activity. Here we examined the effects of locus coeruleus (LC) stimulation on "off-beam" inhibitions of Purkinje cell firing induced by activation of local basket and stellate cell interneurons to determine whether endogenous NE, released from synaptic terminals, could induce a comparable enhancement of GABA-mediated synaptic input to these neurons. Stimulation of LC, at current intensities which by themselves were subthreshold for directly affecting background activity of Purkinje neurons, markedly increased off-beam inhibitory neuronal responses. Iontophoretic application of the beta-adrenergic blocker sotalol reversibly antagonized this enhancement of synaptic inhibition. In comparison, the potentiative effects observed with LC stimulation were increased by iontophoresis of the alpha-adrenergic blocker phentolamine. LC -induced increases in off-beam inhibition were not observed after destruction of cerebellar noradrenergic terminals by 6-hydroxydopamine. These results suggest that noradrenergic input from the LC can augment the efficacy of conventional GABA-mediated inputs synapsing on the Purkinje cell.