{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:02:05Z","timestamp":1791216125357,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2004,4,29]],"date-time":"2004-04-29T00:00:00Z","timestamp":1083196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand\u2010gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic inhibition of GABAergic transmission onto Purkinje cells in the cerebellar cortex. Although presynaptic inhibition is critical for information processing at central synapses, the molecular mechanisms by which AMPARs take part in such actions are not known. This study therefore aimed at further examining the properties of AMPAR\u2010mediated presynaptic inhibition at GABAergic synapses in the rat cerebellum. Our data provide evidence that the climbing fibre\u2010induced inhibition of GABA release from interneurons depends on AMPAR\u2010mediated activation of GTP\u2010binding proteins coupled with down\u2010regulation of presynaptic voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup> channels. A G<jats:sub>i\/o<\/jats:sub>\u2010protein inhibitor, N\u2010ethylmaleimide, selectively abolished the AMPAR\u2010mediated presynaptic inhibition at cerebellar GABAergic synapses but did not affect AMPAR\u2010mediated excitatory actions on Purkinje cells. Furthermore, both G<jats:sub>i\/o<\/jats:sub>\u2010coupled receptor agonists, baclofen and DCG\u2010IV, and the P\/Q\u2010type calcium channel blocker \u03c9\u2010agatoxin IVA markedly occluded the AMPAR\u2010mediated inhibition of GABAergic transmission. Conversely, AMPAR activation inhibited action potential\u2010triggered Ca<jats:sup>2+<\/jats:sup> influx into individual axonal boutons of cerebellar GABAergic interneurons. By suppressing the inhibitory inputs to Purkinje cells, the AMPAR\u2010mediated presynaptic inhibition could thus provide a feed\u2010forward mechanism for the information flow from the cerebellar cortex.<\/jats:p>","DOI":"10.1111\/j.0953-816x.2004.03347.x","type":"journal-article","created":{"date-parts":[[2004,4,29]],"date-time":"2004-04-29T15:53:33Z","timestamp":1083254013000},"page":"2464-2474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["AMPA receptor\u2010mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanisms"],"prefix":"10.1111","volume":"19","author":[{"given":"Shin'Ichiro","family":"Satake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihito","family":"Saitow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Rusakov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Konishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,4,29]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"244","article-title":"Uncoupling of \u03b3\u2010aminobutyric acid B receptors from GTP\u2010binding proteins by N\u2010ethylmaleimide: Effect of N\u2010ethylmaleimide on purified GTP\u2010binding proteins","volume":"29","author":"Asano T.","year":"1986","journal-title":"Mol. 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