{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:34:57Z","timestamp":1791174897480,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T00:00:00Z","timestamp":1392249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council, UK","doi-asserted-by":"crossref","award":["BB\/D018501\/1"],"award-info":[{"award-number":["BB\/D018501\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council, UK","doi-asserted-by":"crossref","award":["BB\/B500958\/1"],"award-info":[{"award-number":["BB\/B500958\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council, UK","doi-asserted-by":"crossref","award":["BB\/J015660\/1"],"award-info":[{"award-number":["BB\/J015660\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Release of neurotransmitter can sometimes occur outside of the synaptic cleft, a process known as ectopic release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Spillover of the excitatory transmitter glutamate between synapses occurs when parallel fibres in the cerebellum are stimulated at high frequencies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We investigated the effect of activity\u2010dependent and pharmacological reduction of ectopic release on the time course of postsynaptic currents and found that the decay time is reduced, suggesting that ectopic release contributes to spillover at the synapses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This finding suggests that ectopic transmission can cause activation of extrasynaptic receptors even at low frequencies, and so may play a significant role in synaptic plasticity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results help us understand how signalling in and around the synapse can alter network activity in the cerebellum, a brain region essential for fine motor coordination.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>In the rat cerebellar molecular layer, spillover of glutamate between parallel fibre synapses can lead to activation of perisynaptic receptors that mediate short\u2010 and long\u2010term plasticity. This effect is greatest when clusters of fibres are stimulated at high frequencies, suggesting that glutamate clearance mechanisms must be overwhelmed before spillover can occur. However, parallel fibres can also release transmitter directly into the extracellular space, from \u2018ectopic\u2019 release sites. Ectopic transmission activates AMPA receptors on the Bergmann glial cell processes that envelop parallel fibre synapses, but the possible contribution of this extrasynaptic release to intersynaptic communication has not been explored. We exploited long\u2010term depression of ectopic transmission, and selective pharmacology, to investigate the impact of these release sites on the time course of Purkinje neuron excitatory postsynaptic currents (EPSCs). Depletion of ectopic release pools by activity\u2010dependent long\u2010term depression decreased EPSC decay time, revealing a \u2018late\u2019 current that is present when fibres are stimulated at low frequencies. This effect was enhanced when glutamate transporters were inhibited, and reduced when extracellular diffusion was impeded. Blockade of N\u2010type Ca<jats:sup>2+<\/jats:sup> channels inhibited ectopic transmission to Bergmann glia and decreased EPSC decay time. Similarly, perfusion of the Ca<jats:sup>2+<\/jats:sup> chelator EGTA\u2010AM into the slice progressively eliminated ectopic transmission to glia and decreased EPSC decay time with closely similar time courses. Collectively, this evidence suggests that ectopically released glutamate contributes to spillover transmission, and that ectopic release therefore degrades the spatial precision of synapses that fire infrequently, and may make them more prone to exhibit plasticity.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2013.267039","type":"journal-article","created":{"date-parts":[[2014,1,14]],"date-time":"2014-01-14T02:54:43Z","timestamp":1389668083000},"page":"1493-1503","source":"Crossref","is-referenced-by-count":13,"title":["Ectopic release of glutamate contributes to spillover at parallel fibre synapses in the cerebellum"],"prefix":"10.1113","volume":"592","author":[{"given":"Saju","family":"Balakrishnan","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Signalling The Babraham Institute Babraham Research Campus  Cambridge CB22 3AT UK"},{"name":"Institute of Neuro &amp; Sensory Physiology  Humboldtallee\u201023 G\u00f6ttingen 37073 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