title: Monoaminergic modulation of GABAergic transmission onto cerebellar globular cells.
abstract: Cerebellar Purkinje cells (PCs) project their axon collaterals to underneath of the PC layer and make GABAergic synaptic contacts with globular cells, a subgroup of Lugaro cells. GABAergic transmission derived from the PC axon collaterals is so powerful that it could inhibit globular cells and regulate their firing patterns. However, the physiological properties and implications of the GABAergic synapses on globular cells remain unknown. Using whole-cell patch-clamp recordings from globular cells in the mouse cerebellum, we examined the monoaminergic modulation of GABAergic inputs to these cells. Application of either serotonin (5-HT) or noradrenaline (NA) excited globular cells, thereby leading to their firing. The 5-HT- and NA-induced firing was temporally confined and attenuated by GABAergic transmission, although 5-HT and NA exerted an inhibitory effect on the release of GABA from presynaptic terminals of PC axon collaterals. Agonists for 5-HT1Breceptors and α2-adrenoceptors mimicked the 5-HT- and NA-induced suppression of GABAergic activity. Through their differential modulatory actions on the cerebellar inhibitory neural circuits, 5-HT facilitated PC firing, whereas NA suppressed it. These results indicate that 5-HT and NA regulate the membrane excitability of globular cells and PCs through their differential modulation of not only the membrane potential but also GABAergic synaptic circuits. Monoaminergic modulation of the neural connections between globular cells and PCs could play a role in cerebellar motor coordination.
authors.affiliation: Organization for Research Initiatives and Development, Doshisha University, Kyoto 610-0394, Japan; Laboratory for Motor Learning Control, RIKEN BSI, Wako 351-0198, Japan. Electronic address: mhirono@mail.doshisha.ac.jp.
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Hirono
authors.affiliation: Laboratory for Motor Learning Control, RIKEN BSI, Wako 351-0198, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Nagao
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Masebashi 371-8511, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Neurophysiology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa 769-2193, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Konishi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015306:Biogenic Monoamines / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D059330:GABAergic Neurons / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015306:Biogenic Monoamines; D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D008164:Luminescent Proteins; D026941:Sodium Channel Blockers; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; C054562:yellow fluorescent protein, Bacteria; D012701:Serotonin; D013779:Tetrodotoxin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D009638:Norepinephrine
keywords: Axon collateral; Cerebellum; GABA; Noradrenaline; Serotonin; Synaptic modulation