title: Noradrenergic modulation of the parallel fiber-Purkinje cell synapse in mouse cerebellum.
abstract: 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 α1-and α2-adrenergic receptors to produce synaptic depression between parallel fibers and Purkinje cells. On the contrary, PF-EPSCs were potentiated by the β-adrenergic receptor agonist isoproterenol. This short-term potentiation was postsynaptically expressed, required protein kinase A, and was mimicked by the β2-adrenoceptor agonist clenbuterol, suggesting that the β2-adrenoceptors mediate the noradrenergic facilitation of synaptic transmission between parallel fibers and Purkinje cells. Moreover, β-adrenoceptor activation lowered the threshold for cerebellar long-term potentiation induced by 1 Hz parallel fiber stimulation. The presence of both α and β 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.
authors.affiliation: Dept. of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Lippiello
authors.affiliation: Dept. of Neuroscience, University of Torino, Torino, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), Italy.
authors.forename: Eriola
authors.initials: E
authors.lastname: Hoxha
authors.affiliation: Dept. of Pharmacy, University of Naples Federico II, Naples, Italy; Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, Naples, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Volpicelli
authors.affiliation: Dept. of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lo Duca
authors.affiliation: Dept. of Neuroscience, University of Torino, Torino, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), Italy. Electronic address: filippo.tempia@unito.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Tempia
authors.affiliation: Dept. of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Miniaci
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D000322:Adrenergic Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2
keywords: Cerebellum; Long-term potentiation; Noradrenaline; Norepinephrine; Purkinje cell; Synaptic modulation; Synaptic transmission