Noradrenergic modulation of the parallel fiber-Purkinje cell synapse in mouse cerebellum

The signals arriving to Purkinje cells via parallel fibers are essential for all tasks in which the cerebellum is involved, including motor control, learning new motor skills and calibration of reflexes. Since learning also requires the activation of adrenergic receptors, we investigated the effects of adrenergic receptor agonists on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that noradrenaline serves as an endogenous ligand for both alpha(1) and alpha(2)-adrenergic receptors to produce synaptic depression between parallel fibers and Purkinje cells. On the contrary, PF-EPSCs were potentiated by the beta-adrenergic receptor agonist isoproterenol. This short-term potentiation was post-synaptically expressed, required protein kinase A, and was mimicked by the beta(2)-adrenoceptor agonist clenbuterol, suggesting that the beta(2)-adrenoceptors mediate the noradrenergic facilitation of synaptic transmission between parallel fibers and Purkinje cells. Moreover, beta-adrenoceptor activation lowered the threshold for cerebellar long-term potentiation induced by 1 Hz parallel fiber stimulation. The presence of both alpha and beta adrenergic receptors on Purkinje cells suggests the existence of bidirectional mechanisms of regulation allowing the noradrenergic afferents to refine the signals arriving to Purkinje cells at particular arousal states or during learning. (C) 2014 Elsevier Ltd. All rights reserved.