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• W2113100660 abstract "Abstract Synaptic plasticity has been studied extensively at excitatory synapses, whereas studies on plasticity at GABAergic inhibitory synapses have been limited. In the rat cerebellar cortex, postsynaptic depolarization of a Purkinje neuron (PN) induces long‐term potentiation of GABA A receptor (GABA A R) responsiveness (termed rebound potentiation; RP). Induction of RP requires an increase in intracellular Ca 2+ concentration and resultant activation of Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII). We previously reported that GABA B receptor (GABA B R) activation coupled with depolarization suppresses RP induction by facilitating protein phosphatase 1 (PP‐1)‐mediated inhibition of CaMKII through down‐regulation of cAMP‐dependent protein kinase A (PKA) activity. Here, we examined the involvement of metabotropic glutamate receptor type 1 (mGluR1) in RP regulation. RP was monitored with the amplitudes of either the current responses to GABA or miniature inhibitory postsynaptic currents recorded from a PN in a primary culture or in a cerebellar slice. Inhibition of mGluR1 by an antagonist, 7(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxylate‐ethyl‐ester (CPCCOEt), prevented RP induction, which was abolished either by activation of adenylyl cyclase or by inhibition of PP‐1. Furthermore, mGluR1 inhibition impaired depolarization‐induced CaMKII activation. By contrast, activation of mGluR1 by the agonist (R,S)3,5‐dihydroxyphenylglycine (DHPG) rescued RP induction from its suppression by GABA B R activation. The rescue was impaired either by inhibition of PKA or by facilitation of PP‐1 activity. In addition, mGluR1 activation counteracted the GABA B R‐mediated CaMKII inhibition. Taken together, these results suggest that mGluR1 activity counteracts GABA B R activity and contributes to RP induction through PKA activation, down‐regulation of PP‐1 and up‐regulation of CaMKII." @default.
• W2113100660 created "2016-06-24" @default.
• W2113100660 creator A5053372897 @default.
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• W2113100660 date "2008-02-01" @default.
• W2113100660 modified "2023-10-10" @default.
• W2113100660 title "mGluR1-mediated facilitation of long-term potentiation at inhibitory synapses on a cerebellar Purkinje neuron" @default.
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• W2113100660 doi "https://doi.org/10.1111/j.1460-9568.2008.06063.x" @default.
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