{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:46:07Z","timestamp":1792158367661,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["EQU202203014705"],"award-info":[{"award-number":["EQU202203014705"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201021\u2010CE14\u20100021\u201001"],"award-info":[{"award-number":["ANR\u201021\u2010CE14\u20100021\u201001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201023\u2010CE14\u20100014\u201002"],"award-info":[{"award-number":["ANR\u201023\u2010CE14\u20100014\u201002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201020\u2010CE14\u20100020"],"award-info":[{"award-number":["ANR\u201020\u2010CE14\u20100020"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201021\u2010CE16\u20100028"],"award-info":[{"award-number":["ANR\u201021\u2010CE16\u20100028"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201019\u2010CE16\u20100001"],"award-info":[{"award-number":["ANR\u201019\u2010CE16\u20100001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201021\u2010NEU2\u20100004\u201001"],"award-info":[{"award-number":["ANR\u201021\u2010NEU2\u20100004\u201001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004795","name":"Institut Universitaire de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Abstract<\/jats:title>\n \n Midbrain dopamine (DA)\u2010neurons are slow pacemakers that continuously fire action potentials, maintaining basal extracellular DA levels in target regions. The sodium leak channel NALCN has been identified as a key contributor in the pacemaker control of these neurons. However, the consequences of a disrupted DA pacemaker activity remain largely unexplored. By generating mice lacking NALCN selectively in midbrain DA\u2010neurons, we investigated the impact of this deletion on the activity of ventral tegmental area DA\u2010neurons, D2R\u2010mediated signalling, reactivity to cues predicting threat and psychostimulant responsiveness in both males and females. Selective deletion of\n NALCN<\/jats:italic>\n in midbrain DA\u2010neurons dampens their tonic activity, without reducing the basal extracellular DA levels in the nucleus accumbens. Mice with a loss of NALCN in DA\u2010neurons exhibit no impairments of basal motor responses, unaltered reactivity to cues predicting threat and risk assessment, while the neurochemical and behavioural responsiveness to psychostimulant drugs are enhanced and presynaptic D2R\u2010mediated signalling at DA terminals is altered. Together, our results emphasize the important role of NALCN conductance in controlling DA pacemaker activity, D2R\u2010mediated signalling and in modulating motor responses to psychostimulants.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n The sodium leak channel NALCN is an important contributor to the spontaneous pacemaker activity in dopamine neurons, but the consequences of its loss in these neurons remain largely unknown.<\/jats:p>\n <\/jats:list-item>\n \n We investigated how selective deletion of NALCN in dopamine neurons affects neuronal activity, dopamine receptor signalling and behavioural responses in male and female mice.<\/jats:p>\n <\/jats:list-item>\n \n Loss of NALCN markedly reduced the spontaneous activity of dopamine neurons, yet basal motor function, reward\u2010related responses and reactivity to threat\u2010predicting cues remained largely preserved.<\/jats:p>\n <\/jats:list-item>\n \n In contrast, neurochemical and behavioural responsiveness to psychostimulant drugs are enhanced, probably through an altered presynaptic D2R\u2010mediated signalling at DA terminals.<\/jats:p>\n <\/jats:list-item>\n \n NALCN emerges as a key regulator of dopamine neuron activity, with disrupted pacemaker firing selectively enhancing psychostimulant sensitivity.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289809","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:45:44Z","timestamp":1791305144000},"page":"8542-8568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deletion of the sodium leak channel NALCN in dopamine neurons alters D2R\u2010mediated signalling and psychostimulant responsiveness"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-0277","authenticated-orcid":false,"given":"Angelina","family":"Rogliardo","sequence":"first","affiliation":[{"name":"INM University Montpellier, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinaig Le","family":"Borgne","sequence":"additional","affiliation":[{"name":"Plasticit\u00e9 du Cerveau CNRS UMR8249 \u00c9cole sup\u00e9rieure de physique et de chimie industrielles de la Ville de Paris (ESPCI) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Gulmez","sequence":"additional","affiliation":[{"name":"Plasticit\u00e9 du Cerveau CNRS UMR8249 \u00c9cole sup\u00e9rieure de physique et de chimie industrielles de la Ville de Paris (ESPCI) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1375-9572","authenticated-orcid":false,"given":"Adeline","family":"Cathala","sequence":"additional","affiliation":[{"name":"Neurocentre Magendie, U1215 University Bordeaux, INSERM Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6426-7721","authenticated-orcid":false,"given":"Claire","family":"Naon","sequence":"additional","affiliation":[{"name":"INM University Montpellier, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1018-4910","authenticated-orcid":false,"given":"Audrey","family":"Mignon","sequence":"additional","affiliation":[{"name":"INM University Montpellier, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00eblle","family":"Avrillon","sequence":"additional","affiliation":[{"name":"INM University Montpellier, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nejmeh","family":"Mashhour","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative Universit\u00e9 Paris Cit\u00e9, CNRS Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Castell","sequence":"additional","affiliation":[{"name":"IGF University Montpellier, CNRS, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bernat","sequence":"additional","affiliation":[{"name":"IGF University Montpellier, CNRS, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Revest","sequence":"additional","affiliation":[{"name":"Neurocentre Magendie, U1215 University Bordeaux, INSERM Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Monteil","sequence":"additional","affiliation":[{"name":"IGF University Montpellier, CNRS, Inserm Montpellier France"},{"name":"Department of Physiology, Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Faure","sequence":"additional","affiliation":[{"name":"Plasticit\u00e9 du Cerveau CNRS UMR8249 \u00c9cole sup\u00e9rieure de physique et de chimie industrielles de la Ville de Paris (ESPCI) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Bertaso","sequence":"additional","affiliation":[{"name":"INM University Montpellier, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-2139","authenticated-orcid":false,"given":"Giuseppe","family":"Gangarossa","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative Universit\u00e9 Paris Cit\u00e9, CNRS Paris France"},{"name":"Institut Universitaire de France (IUF) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-457X","authenticated-orcid":false,"given":"Fabio","family":"Marti","sequence":"additional","affiliation":[{"name":"Plasticit\u00e9 du Cerveau CNRS UMR8249 \u00c9cole sup\u00e9rieure de physique et de chimie industrielles de la Ville de Paris (ESPCI) Paris France"},{"name":"Neuroscience Paris Seine CNRS UMR 8246 INSERM U1130, Institut de Biologie Paris Seine Sorbonne Universit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1034-606X","authenticated-orcid":false,"given":"Emmanuel","family":"Valjent","sequence":"additional","affiliation":[{"name":"INM University Montpellier, Inserm Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0918-12.2012"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06864.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08167.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2862"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.228"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.11.022"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2023.110883"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-026-02363-9"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2022.103750"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-873"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0930-22.2023"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00132"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12995"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.60"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39805-7"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.87902"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2024.10.001"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.036"},{"key":"e_1_2_5_20_1","unstructured":"Franklin K. &Paxinos G.(2008).The Mouse Brain in Stereotaxic Coordinates.3rd ed.Academic Press."},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00192-2"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021317-121615"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(96)00052-5"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/379606a0"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(89)90440-1"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.036079.114"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP283716"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.150028"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108722"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.028"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.08969"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg8869"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0143-10.2010"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2237-08.2008"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2000.01443.x"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0742470.x"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.20.5715"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.10.004"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07579"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04784-7"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.138"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3101-18.2019"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21519"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40984"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15716-9"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4341-06.2007"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301663"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.03.003"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.08.025"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2015.26"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.1.1"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.042"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.07.019"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.62051750.x"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007032"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.70920"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ads6004"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2019.01.004"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187698"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88319"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-10-03443.2001"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58382-5"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2808"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813415106"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289809","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP289809","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:53:08Z","timestamp":1792155188000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP289809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":63,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1113\/JP289809"],"URL":"https:\/\/doi.org\/10.1113\/jp289809","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}