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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 585/2/549    most recent jphysiol.2007.141010v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kamikubo, Y. Articles by Kano, M. Search for Related Content PubMed PubMed Citation Articles by Kamikubo, Y. Articles by Kano, M. Related Collections Neuroscience Related Article

¹ Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
² Laboratory of Synaptic Plasticity, Graduate School of Frontier Biosciences, Osaka University, Machikaneyama-cho 1-1, Toyonaka, Osaka 560-0043, Japan
³ Department of Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
⁴ Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Hakkaido 060-8638, Japan
⁵ Department of Neurophysiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-kv, Tokyo 113-0033, Japan

Long-term depression (LTD) of excitatory transmission at cerebellar parallel fibre–Purkinje cell synapses is a form of synaptic plasticity crucial for cerebellar motor learning. Around the postsynaptic membrane of these synapses, B-type -aminobutyric acid receptor (GABA_BR), a G_i/o protein-coupled receptor for the inhibitory transmitter GABA is concentrated and closely associated with type-1 metabotropic glutamate receptors (mGluR1) whose signalling is a key factor for inducing LTD. We found that in cultured Purkinje cells, GABA_BR activation enhanced LTD of a glutamate-evoked current (LTD_glu), increasing the magnitude of depression. It has been reported that parallel fibre–Purkinje cell synapses receive a micromolar level of GABA spilt over from the synaptic terminals of the neighbouring GABAergic interneurons. This level of GABA was able to enhance LTD_glu. Our pharmacological analyses revealed that the β subunits but not the subunit of G_i/o protein mediated GABA_BR-mediated LTD_glu enhancement. G_i/o protein activation was sufficient to enhance LTD_glu. In this respect, LTD_glu enhancement is clearly distinguished from the previously reported GABA_BR-mediated augmentation of an mGluR1-coupled slow excitatory postsynaptic potential. Baclofen application for only the induction period of LTD_glu was sufficient to enhance LTD_glu, suggesting that GABA_BR signalling may modulate mechanisms underlying LTD_glu induction. Baclofen augmented mGluR1-coupled Ca²⁺ release from the intracellular stores in a G_i/o protein-dependent manner. Therefore, GABA_BR-mediated LTD_glu enhancement is likely to result from augmentation of mGluR1 signalling. Furthermore, pharmacological inhibition of GABA_BR reduced the magnitude of LTD at parallel fibre–Purkinje cell synapses in cerebellar slices. These findings demonstrate a novel mechanism that would facilitate cerebellar motor learning.

(Received 20 July 2007; accepted after revision 12 October 2007; first published online 18 October 2007)
Corresponding author M. Kano: Department of Neurophysiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Email: mkano-tky{at}m.u-tokyo.ac.jp

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