Potentiation of GABA inhibitory action in cerebrllum by locus coeruleus stimulation

Abstract

In cerebellum, excitatory and inhibitory responses of Purkinje cells, produced both synaptically and by microiontophoresis of putative amino acid neurotransmitters, have been shown previously to be enhanced during NE iontophoresis. The influence of locus coeruleus conditioning stimulation on Purkinje cell responses to GABA iontophoresis was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar modulatory effects. Locus coeruleus stimulation at current intensities which alone elicited no direct depression of Purkinje cell spontaneous discharge potentiated the inhibition produced by GABA. Iontophoretic application of sotalol, a specific beta-adrenergic blocker, antagonized this enhancement of GABA inhibition. Repetitive activation of the classic non-adrenergic cerebellar afferents did not enhance the GABA response, despite causing a direct depression in spontaneous rate. A neuromodulatory role is suggested for tonic adrenergic input in the mammalian central nervous system.