{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:22:53Z","timestamp":1788780173776,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2008,9,15]],"date-time":"2008-09-15T00:00:00Z","timestamp":1221436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2008,9,15]]},"abstract":"<jats:p>Loss\u2010of\u2010function mutations in the gene encoding P\/Q\u2010type Ca<jats:sup>2+<\/jats:sup> channels cause cerebellar ataxia in mice and humans, but the underlying mechanism(s) are unknown. These Ca<jats:sup>2+<\/jats:sup> channels play important roles in regulating both synaptic transmission and intrinsic membrane properties, and defects in either could contribute to ataxia. Our previous work described changes in intrinsic properties and excitability of cerebellar Purkinje cells (PCs) resulting from the <jats:italic>leaner<\/jats:italic> mutation, which is known to reduce whole\u2010cell Ca<jats:sup>2+<\/jats:sup> currents in PCs and cause severe ataxia. Here we describe the impact of this mutation on excitatory synaptic transmission from parallel and climbing fibres (PFs, CFs) to PCs in acute cerebellar slices. We found that in <jats:italic>leaner<\/jats:italic> PCs, PF\u2010evoked excitatory postsynaptic currents (PF\u2010EPSCs) are \u223c50% smaller, and CF\u2010evoked EPSCs are \u223c80% larger, than in wild\u2010type (WT) mice. To investigate whether reduced presynaptic Ca<jats:sup>2+<\/jats:sup> entry plays a role in attenuating PF\u2010EPSCs in <jats:italic>leaner<\/jats:italic> mice, we examined paired\u2010pulse facilitation (PPF). We found that PPF is enhanced in <jats:italic>leaner<\/jats:italic>, suggesting that reduced presynaptic Ca<jats:sup>2+<\/jats:sup> entry reduces neurotransmitter release at these synapses. Short\u2010term plasticity was unchanged at CF\u2013PC synapses, suggesting that CF\u2010EPSCs are larger in <jats:italic>leaner<\/jats:italic> PCs because of increased synapse number or postsynaptic sensitivity, rather than enhanced presynaptic Ca<jats:sup>2+<\/jats:sup> entry. To investigate the functional impact of the observed EPSC changes, we also compared excitatory postsynaptic potentials (EPSPs) elicited by PF and CF stimulation in WT and <jats:italic>leaner<\/jats:italic> PCs. Importantly, we found that despite pronounced changes in PF\u2010 and CF\u2010EPSCs, evoked EPSPs in <jats:italic>leaner<\/jats:italic> mice are very similar to those observed in WT animals. These results suggest that changes in synaptic currents and intrinsic properties of PCs produced by the <jats:italic>leaner<\/jats:italic> mutation together maintain PC responsiveness to excitatory synaptic inputs. They also implicate other consequences of the <jats:italic>leaner<\/jats:italic> mutation as causes of abnormal cerebellar motor control in mutant mice.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.156232","type":"journal-article","created":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:25:02Z","timestamp":1217550302000},"page":"4501-4515","source":"Crossref","is-referenced-by-count":21,"title":["Impact of the <i>leaner<\/i> P\/Q\u2010type Ca<sup>2+<\/sup> channel mutation on excitatory synaptic transmission in cerebellar Purkinje cells"],"prefix":"10.1113","volume":"586","author":[{"given":"Shaolin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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