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The granule cell axon is made of an ascending portion and a long parallel fibre extending at right angles, an architecture suggesting that synapses formed by the two segments of the axon could encode different information. There are controversial indications that ascending axon (AA) and parallel fibre (PF) synapse properties and modalities of plasticity are different. We tested the hypothesis that AA and PF synapses encode different information, and that the association of these distinct inputs to Purkinje cells might be relevant to the circuit and trigger plasticity, similar to the coincident activation of PF and climbing fibre inputs. Here, by recording synaptic currents in Purkinje cells from either proximal or distal granule cells (mostly AA and PF synapses, respectively), we describe a new form of associative plasticity between these two distinct granule cell inputs. We show for the first time that synchronous AA and PF repetitive train stimulation, with inhibition intact, triggers long-term potentiation (LTP) at AA synapses specifically. Furthermore, the timing of the presentation of the two inputs controls the outcome of plasticity and induction requires NMDAR and mGluR1 activation. The long length of the PFs allows us to preferentially activate the two inputs independently, and despite a lack of morphological reconstruction of the connections, these observations reinforce the suggestion that AA and PF synapses have different coding capabilities and plasticity that is associative, enabling effective association of information transmitted via granule cells.<\/jats:p>","DOI":"10.7554\/elife.96140","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T11:42:41Z","timestamp":1713267761000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.96140","source":"Crossref","is-referenced-by-count":1,"title":["Associative plasticity of granule cell inputs to cerebellar Purkinje cells"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-2087","authenticated-orcid":true,"given":"Rossella","family":"Conti","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Saints-P\u00e8res Paris Institute for the Neurosciences","place":["Paris, 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Associative plasticity of granule cell inputs to cerebellar Purkinje cells. 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