title: mGluR1-mediated facilitation of long-term potentiation at inhibitory synapses on a cerebellar Purkinje neuron.
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.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Kawaguchi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D054645:Protein Phosphatase 1 / Q000378:metabolism; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D002867:Chromones; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054645:Protein Phosphatase 1; C010117:3,4-dihydroxyphenylglycol