title: Interneuron- and GABA(A) receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells.
abstract: Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABA(A) receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABA(A) receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABA(A) receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABA(A) receptors and is abolished by preventing CaMKII phosphorylation of GABA(A) receptors. Our results reveal a novel GABA(A) receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Qionger
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Duguid
authors.affiliation: Wolfson Institute for Biomedical Research, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Beverley
authors.initials: B
authors.lastname: Clark
authors.affiliation: Department of Neuroscience Rita Levi Montalcini, University of Turin, 15-10126 Turin, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Panzanelli
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Bijal
authors.initials: B
authors.lastname: Patel
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Institute of Pharmacology, University of Zurich, Winterthurestrasse 190, Zurich 8057, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Fritschy
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Smart
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D017774:Long-Term Potentiation; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011689:Purkinje Cells / Q000378:metabolism*; D018079:Receptors, GABA / Q000235:genetics* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism
chemical_list: C470436:Gabrb2 protein, mouse; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium