Locus coeruleus stimulation potentiates Purkinje cell responses to afferent input: the climbing fiber system

In cerebellum, the evoked responses of the Purkinje cell to both excitatory and inhibitory afferent input have previously been shown to be enhanced by local iontophoresis of norepinephrine (NE). The influence of locus coeruleus (LC) conditioning stimulation on Purkinje cell responses to climbing fiber input was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar potentiative effects. Stimulation of LC, at intensities which by themselves were subthreshold for directly affecting background activity, markedly enhanced complex spike excitation of Purkinje cells elicited by activation of climbing fiber inputs from sensorimotor cortex. Depressant responses observed after complex spike excitation were also augmented by the LC conditioning. Iontophoretic application of sotalol, a specific beta-adrenergic receptor blocker, reversibly antagonized this facilitation of climbing fiber-evoked responses. In addition, the potentiative effects of LC stimulation were not observed after destruction of NE-containing axons and terminals in cerebellum by 6-OHDA. These results suggest that noradrenergic input from the LC can enhance the efficacy of climbing fiber synaptic action on the Purkinje cell, and are thus consistent with the hypothesis of a 'modulatory' role rather than a specific information transfer function for NE in cerebellum.