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Despite intense work, the extent and physiological role for subthreshold synaptic activity reaching the presynaptic boutons has remained elusive because of the technical limitation to record from them. To address this issue, we made simultaneous patch-clamp recordings from the presynaptic varicosities of cerebellar GABAergic interneurons together with their parent soma or postsynaptic target cells in young rat slices and\/or primary cultures. Our\n                    <jats:italic>tour-de-force<\/jats:italic>\n                    direct functional dissection indicates that the somatodendritic spontaneous excitatory synaptic potentials are transmitted down the axon for significant distances, depolarizing presynaptic boutons. These analogously transmitted excitatory synaptic potentials augment presynaptic Ca\n                    <jats:sup>++<\/jats:sup>\n                    influx upon arrival of an immediately following AP through a mechanism that involves a voltage-dependent priming of the Ca\n                    <jats:sup>++<\/jats:sup>\n                    channels, leading to an increase in GABA release, without any modification in the presynaptic AP waveform or residual Ca\n                    <jats:sup>++<\/jats:sup>\n                    . Our work highlights the role of the axon in synaptic integration.\n                  <\/jats:p>","DOI":"10.7554\/elife.85971","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T05:32:27Z","timestamp":1687411947000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85971","source":"Crossref","is-referenced-by-count":7,"title":["Analogue signaling of somatodendritic synaptic activity to axon enhances GABA release in young cerebellar molecular layer interneurons"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6704-7303","authenticated-orcid":true,"given":"Federico","family":"Trigo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05b50ej63","id-type":"ROR","asserted-by":"publisher"}],"name":"Departamento de Neurofisiolog\u00eda Celular y Molecular, Instituto de Investigaciones Biol\u00f3gicas Clemente Estable","place":["Montevideo, Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8386-1185","authenticated-orcid":true,"given":"Shin-ya","family":"Kawaguchi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02kpeqv85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biophysics, Graduate School of Science, Kyoto University Oiwake-cho","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1126\/science.1119055","article-title":"Combined analog and action potential coding in hippocampal mossy fibers","volume":"311","author":"Alle","year":"2006","journal-title":"Science"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"8001","DOI":"10.1523\/JNEUROSCI.0972-11.2011","article-title":"Sparse but highly efficient Kv3 outpace BKCa channels in action potential repolarization at hippocampal mossy fiber boutons","volume":"31","author":"Alle","year":"2011","journal-title":"The Journal of Neuroscience"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.cell.2004.10.004","article-title":"Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment","volume":"119","author":"Ango","year":"2004","journal-title":"Cell"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12102","article-title":"Action potential broadening in a presynaptic channelopathy","volume":"7","author":"Begum","year":"2016","journal-title":"Nature Communications"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201912523","article-title":"Differentially poised vesicles underlie fast and slow components of release at single synapses","volume":"152","author":"Blanchard","year":"2020","journal-title":"The Journal of General Physiology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nn.3624","article-title":"Ultra-rapid axon-axon ephaptic inhibition of cerebellar Purkinje cells by the pinceau","volume":"17","author":"Blot","year":"2014","journal-title":"Nature Neuroscience"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1098\/rstb.1999.0386","article-title":"Effect of changes in action potential shape on calcium currents and transmitter release in a calyx-type synapse of the rat auditory brainstem","volume":"354","author":"Borst","year":"1999","journal-title":"Philosophical Transactions of the Royal Society of London. 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