title: Alpha-adrenoceptive dual modulation of inhibitory GABAergic inputs to Purkinje cells in the mouse cerebellum.
abstract: Noradrenaline (NA) modulates synaptic transmission in various sites of the CNS. In the cerebellar cortex, several studies have revealed that NA enhances inhibitory synaptic transmission by beta-adrenoceptor-and cyclic AMP-dependent pathways. However, the effects of alpha-adrenoceptor activation on cerebellar inhibitory neurotransmission have not yet been fully elucidated. Therefore we investigated the effects of the alpha1- or alpha2-adrenoceptor agonist on inhibitory postsynaptic currents (IPSCs) recorded from mouse Purkinje cells (PCs). We found that the nonselective alpha-adrenoceptor agonist 6-fluoro-norepinephrine increased both the frequency and amplitude of spontaneous IPSCs (sIPSCs). This enhancement was mostly mimicked by the selective alpha1-adrenoceptor agonist phenylephrine (PE). PE also enhanced the amplitude of evoked IPSCs (eIPSCs) and increased the frequency but not the amplitude of miniature IPSCs (mIPSCs). Moreover, PE decreased the paired-pulse ratio of eIPSCs and did not change gamma-aminobutyric acid (GABA) receptor sensitivity in PCs. Conversely, the selective alpha2-adrenoceptor agonist clonidine significantly reduced both the frequency and the amplitude of sIPSCs. Neither eIPSCs nor mIPSCs were affected by clonidine. Furthermore, presynaptic cell-attached recordings showed that spontaneous activity of GABAergic interneurons was enhanced by PE but reduced by clonidine. These results suggest that NA enhances inhibitory neurotransmitter release by alpha1-adrenoceptors, which are expressed in presynaptic terminals and somatodendritic domains, whereas NA suppresses the excitability of interneurons by alpha2-adrenoceptors, which are expressed in presynaptic somatodendritic domains. Thus cerebellar alpha-adrenoceptors play roles in a presynaptic dual modulation of GABAergic inputs from interneurons to PCs, thereby providing a likely mechanism for the fine-tuning of information flow in the cerebellar cortex.
authors.affiliation: Neuronal Circuit Mechanisms Research Group, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan. hironom@brain.riken.jp
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Hirono
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Obata
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D011942:Receptors, Adrenergic, alpha; D005680:gamma-Aminobutyric Acid