{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:09:53Z","timestamp":1785413393204,"version":"3.56.0"},"reference-count":67,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Neurons of the inferior olive (IO) fire action potentials with large, long\u2010lasting afterdepolarizations (ADPs). Broader ADPs support more spikes in climbing fibre axons and evoke longer bursts of complex spikes in Purkinje cells, which affect the magnitude and sign of cerebellar synaptic plasticity. In the present study, we investigated the ionic mechanisms that regulate IO action potential waveforms by making whole\u2010cell recordings in brainstem slices from C57BL6\/J mice. IO spikes evoked from rest had ADPs of \u223c30 ms. After 500\u2010ms hyperpolarizations, however, evoked action potentials were brief (1\u20132\u00a0ms), lacking ADPs altogether. Because such preconditioning should maximally recruit depolarizing\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>h<\/jats:sub>\n                      and T\u2010type currents and minimize repolarizing Ca\u2010dependent currents known to shape the ADP, the rapid action potential downstroke suggested additional, dominant recovery of voltage\u2010gated K currents at negative voltages. Under voltage clamp, outward currents evoked from \u201398 mV included large, voltage\u2010gated, rapidly inactivating \u2018A\u2010type\u2019 K currents. These currents had a steep availability curve with half\u2010inactivation at \u201385 mV, suitable for recruitment by small hyperpolarizations. The fast decay time constant increased with depolarization, as is typical of K\n                      <jats:sub>V<\/jats:sub>\n                      4 channels. The K\n                      <jats:sub>V<\/jats:sub>\n                      4 channel blocker AmmTx3 almost eliminated inactivating currents and broadened action potentials evoked from strongly negative potentials by \u223c8\u2010fold. Optogenetic stimulation of inhibitory cerebellar nucleo\u2010olivary terminals hyperpolarized IO cells sufficiently to abolish the ADP. The data support the idea that currents through K\n                      <jats:sub>V<\/jats:sub>\n                      4 channels control action potential waveforms in IO cells, shortening ADPs during synaptic inhibition or troughs of membrane potential oscillations, thereby controlling the number of climbing fibre action potentials that propagate to the cerebellum.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16312-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Neurons in the mouse inferior olive (IO) express a large, inactivating, voltage\u2010gated A\u2010type K current carried by K\n                            <jats:sub>V<\/jats:sub>\n                            4 channels.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>IO action potentials evoked from rest have large, long afterdepolarizations that disappear with pre\u2010spike hyperpolarizations of 5\u201315\u00a0mV.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The steep voltage\u2010sensitivity and rapid recovery of K\n                            <jats:sub>V<\/jats:sub>\n                            4 channels regulates the duration of the afterdepolarization over more than one order of magnitude.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Factors such as synaptic inhibition are sufficient to recruit K\n                            <jats:sub>V<\/jats:sub>\n                            4 channels and eliminate afterdepolarization (ADP).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            By controlling the ADP, K\n                            <jats:sub>V<\/jats:sub>\n                            4 channels can set the number of climbing fibre action potentials relayed to the cerebellum and regulate plasticity implicated in motor learning.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286818","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T15:22:46Z","timestamp":1726845766000},"page":"6269-6284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Control of action potential afterdepolarizations in the inferior olive by inactivating A\u2010type currents through K\n                    <sub>V<\/sub>\n                    4 channels"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-7300","authenticated-orcid":false,"given":"Ziyad W.","family":"Sultan","sequence":"first","affiliation":[{"name":"Department of Neurobiology Northwestern University  Evanston IL USA"},{"name":"Northwestern University Interdepartmental Neuroscience Program Northwestern University  Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-8208","authenticated-orcid":false,"given":"Marion","family":"Najac","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Northwestern University  Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-8177","authenticated-orcid":false,"given":"Indira M.","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Northwestern University  Evanston IL USA"},{"name":"Northwestern University Interdepartmental Neuroscience Program Northwestern University  Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.150540"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2493"},{"key":"e_1_2_5_4_1","article-title":"Slice it hot: Acute adult brain slicing in physiological temperature","volume":"92","author":"Ankri L.","year":"2014","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.77.6.3145"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-12-03862.1996"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2012.00091"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00192"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.04.018"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.184705"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5187-06.2007"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb11293.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009365"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1970.33.2.199"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-11-04700.2003"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903210402"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01673258"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.069"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273424"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1952.sp004764"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/43119"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54073"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.12.030189.000505"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0935-07.2007"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.06.011"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-015-0722-4"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.032"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4664-05.2006"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.05.026"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00588-X"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018095"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00370618"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.1.255"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.032"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1974.37.3.560"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1981.sp013763"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1981.sp013764"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-24-10898.2002"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83239"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.248831"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2559-07.2007"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.023"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.053"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-16-07140.1999"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/416330a"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3583-14.2015"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274598"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.02.001"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03663"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019220"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002995107"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1990.0074"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23435"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-09-03124.1998"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1974.37.3.541"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.08.008"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4495-15.2016"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607888103"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.03294.x"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902880102"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01387-4"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24993"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017079108"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13282"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22866"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.18433\/J3W595"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.08.010"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP286818","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP286818","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP286818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:15:10Z","timestamp":1773119710000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP286818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":67,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1113\/JP286818"],"URL":"https:\/\/doi.org\/10.1113\/jp286818","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,20]]},"assertion":[{"value":"2024-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}