{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:34:06Z","timestamp":1790922846154,"version":"4.1.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG-21-851219"],"award-info":[{"award-number":["AARG-21-851219"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"DOI":"10.1038\/s41398-025-03588-w","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:34:10Z","timestamp":1759732450000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Optogenetic stimulation of midbrain dopaminergic neurons rescues hippocampal synaptic plasticity deficits in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Serena","family":"Ficch\u00ec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Cauzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4556-4451","authenticated-orcid":false,"given":"Livia","family":"La Barbera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"De Paolis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Loffredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6555-785X","authenticated-orcid":false,"given":"Elena","family":"Spoleti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Saba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Biamonte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8369-1561","authenticated-orcid":false,"given":"Annalisa","family":"Nobili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Krashia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6526-1832","authenticated-orcid":false,"given":"Marcello","family":"D\u2019Amelio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"3588_CR1","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nrn3381","volume":"14","author":"SJ Russo","year":"2013","unstructured":"Russo SJ, Nestler EJ. The brain reward circuitry in mood disorders. Nat Rev Neurosci. 2013;14:609\u201325.","journal-title":"Nat Rev Neurosci"},{"key":"3588_CR2","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1016\/j.celrep.2016.01.070","volume":"14","author":"JI Broussard","year":"2016","unstructured":"Broussard JI, Yang K, Levine AT, Tsetsenis T, Jenson D, Cao F, et al. Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the hippocampus. Cell Rep. 2016;14:1930\u20139.","journal-title":"Cell Rep"},{"key":"3588_CR3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2402356122","volume":"122","author":"H Hagena","year":"2025","unstructured":"Hagena H, Manahan-Vaughan D. Oppositional and competitive instigation of hippocampal synaptic plasticity by the VTA and locus coeruleus. Proc Natl Acad Sci USA. 2025;122:e2402356122.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3588_CR4","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1038\/nn.3843","volume":"17","author":"CG McNamara","year":"2014","unstructured":"McNamara CG, Tejero-Cantero \u00c1, Trouche S, Campo-Urriza N, Dupret D. Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence. Nat Neurosci. 2014;17:1658\u201360.","journal-title":"Nat Neurosci"},{"key":"3588_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47481-4","volume":"15","author":"FJP Sayegh","year":"2024","unstructured":"Sayegh FJP, Mouledous L, Macri C, Pi Macedo J, Lejards C, Rampon C, et al. Ventral tegmental area dopamine projections to the hippocampus trigger long-term potentiation and contextual learning. Nat Commun. 2024;15:4100.","journal-title":"Nat Commun"},{"key":"3588_CR6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111069118","volume":"118","author":"T Tsetsenis","year":"2021","unstructured":"Tsetsenis T, Badyna JK, Wilson JA, Zhang X, Krizman EN, Subramaniyan M, et al. Midbrain dopaminergic innervation of the hippocampus is sufficient to modulate formation of aversive memories. Proc Natl Acad Sci USA. 2021;118:e2111069118.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3588_CR7","doi-asserted-by":"publisher","first-page":"14835","DOI":"10.1073\/pnas.1616515114","volume":"113","author":"KA Kempadoo","year":"2016","unstructured":"Kempadoo KA, Mosharov EV, Choi SJ, Sulzer D, Kandel ER. Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory. Proc Natl Acad Sci. 2016;113:14835\u201340.","journal-title":"Proc Natl Acad Sci"},{"key":"3588_CR8","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nature19325","volume":"537","author":"T Takeuchi","year":"2016","unstructured":"Takeuchi T, Duszkiewicz AJ, Sonneborn A, Spooner PA, Yamasaki M, Watanabe M, et al. Locus coeruleus and dopaminergic consolidation of everyday memory. Nature. 2016;537:357\u201362.","journal-title":"Nature"},{"key":"3588_CR9","doi-asserted-by":"publisher","first-page":"6072","DOI":"10.1523\/JNEUROSCI.6486-11.2012","volume":"32","author":"CC Smith","year":"2012","unstructured":"Smith CC, Greene RW. CNS dopamine transmission mediated by noradrenergic innervation. J Neurosci. 2012;32:6072\u201380.","journal-title":"J Neurosci"},{"key":"3588_CR10","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1038\/s41380-024-02408-9","volume":"29","author":"E Spoleti","year":"2024","unstructured":"Spoleti E, La Barbera L, Cauzzi E, De Paolis ML, Saba L, Marino R, et al. Dopamine neuron degeneration in the Ventral Tegmental Area causes hippocampal hyperexcitability in experimental Alzheimer\u2019s disease. Mol Psychiatry. 2024;29:1265\u201380.","journal-title":"Mol Psychiatry"},{"key":"3588_CR11","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13024-022-00580-6","volume":"17","author":"L La Barbera","year":"2022","unstructured":"La Barbera L, Nobili A, Cauzzi E, Paoletti I, Federici M, Saba L, et al. Upregulation of Ca2+-binding proteins contributes to VTA dopamine neuron survival in the early phases of Alzheimer\u2019s disease in Tg2576 mice. Mol Neurodegener. 2022;17:76.","journal-title":"Mol Neurodegener"},{"key":"3588_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113969","volume":"350","author":"E Spoleti","year":"2022","unstructured":"Spoleti E, Krashia P, La Barbera L, Nobili A, Lupascu CA, Giacalone E, et al. Early derailment of firing properties in CA1 pyramidal cells of the ventral hippocampus in an Alzheimer\u2019s disease mouse model. Exp Neurol. 2022;350:113969.","journal-title":"Exp Neurol"},{"key":"3588_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2021.102031","volume":"202","author":"L La Barbera","year":"2021","unstructured":"La Barbera L, Vedele F, Nobili A, Krashia P, Spoleti E, Latagliata EC, et al. Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer\u2019s disease. Prog Neurobiol. 2021;202:102031.","journal-title":"Prog Neurobiol"},{"key":"3588_CR14","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.nbd.2018.05.006","volume":"116","author":"A Cordella","year":"2018","unstructured":"Cordella A, Krashia P, Nobili A, Pignataro A, La Barbera L, Viscomi MT, et al. Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer\u2019s disease. Neurobiol Dis. 2018;116:142\u201354.","journal-title":"Neurobiol Dis"},{"key":"3588_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14727","volume":"8","author":"A Nobili","year":"2017","unstructured":"Nobili A, Latagliata EC, Viscomi MT, Cavallucci V, Cutuli D, Giacovazzo G, et al. Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer\u2019s disease. Nat Commun. 2017;8:14727.","journal-title":"Nat Commun"},{"key":"3588_CR16","doi-asserted-by":"publisher","first-page":"6440","DOI":"10.2174\/1381612811319360005","volume":"19","author":"V Cavallucci","year":"2013","unstructured":"Cavallucci V, Ferraina C, D\u2019Amelio M. Key role of mitochondria in Alzheimer\u2019s disease synaptic dysfunction. Curr Pharm Des. 2013;19:6440\u201350.","journal-title":"Curr Pharm Des"},{"key":"3588_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.315","volume":"6","author":"J-R Hao","year":"2015","unstructured":"Hao J-R, Sun N, Lei L, Li X-Y, Yao B, Sun K, et al. L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer\u2019s disease via activating dopamine D1 receptor\/PKA signaling pathway. Cell Death Dis. 2015;6:e1965.","journal-title":"Cell Death Dis"},{"key":"3588_CR18","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1101\/lm.026070.112","volume":"19","author":"K Guzm\u00e1n-Ramos","year":"2012","unstructured":"Guzm\u00e1n-Ramos K, Moreno-Castilla P, Castro-Cruz M, McGaugh JL, Mart\u00ednez-Coria H, LaFerla FM, et al. Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer\u2019s disease. Learn Mem Cold Spring Harb N. 2012;19:453\u201360.","journal-title":"Learn Mem Cold Spring Harb N"},{"key":"3588_CR19","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/ana.22319","volume":"69","author":"E Himeno","year":"2011","unstructured":"Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, et al. Apomorphine treatment in Alzheimer mice promoting amyloid-\u03b2 degradation. Ann Neurol. 2011;69:248\u201356.","journal-title":"Ann Neurol"},{"key":"3588_CR20","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1074\/jbc.M110.177790","volume":"286","author":"S J\u00fcrgensen","year":"2011","unstructured":"J\u00fcrgensen S, Antonio LL, Mussi GEA, Brito-Moreira J, Bomfim TR, De Felice FG, et al. Activation of D1\/D5 dopamine receptors protects neurons from synapse dysfunction induced by amyloid-beta oligomers. J Biol Chem. 2011;286:3270\u20136.","journal-title":"J Biol Chem"},{"key":"3588_CR21","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.neurobiolaging.2007.11.010","volume":"30","author":"O Ambr\u00e9e","year":"2009","unstructured":"Ambr\u00e9e O, Richter H, Sachser N, Lewejohann L, Dere E, de Souza Silva MA, et al. Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer\u2019s disease. Neurobiol Aging. 2009;30:1192\u2013204.","journal-title":"Neurobiol Aging"},{"key":"3588_CR22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2208254119","volume":"119","author":"DK G\u00e1lvez-M\u00e1rquez","year":"2022","unstructured":"G\u00e1lvez-M\u00e1rquez DK, Salgado-M\u00e9nez M, Moreno-Castilla P, Rodr\u00edguez-Dur\u00e1n L, Escobar ML, Tecuapetla F, et al. Spatial contextual recognition memory updating is modulated by dopamine release in the dorsal hippocampus from the locus coeruleus. Proc Natl Acad Sci USA. 2022;119:e2208254119.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3588_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.1039725","volume":"13","author":"P Krashia","year":"2022","unstructured":"Krashia P, Spoleti E, D\u2019Amelio M. The VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer\u2019s disease. Front Psychiatry. 2022;13:1039725.","journal-title":"Front Psychiatry"},{"key":"3588_CR24","unstructured":"Paxinos G, Franklin KBJ. Paxinos and Franklin\u2019s the Mouse Brain in Stereotaxic Coordinates. 5th Edition. Elsevier\/Academic Press; 2019."},{"key":"3588_CR25","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.expneurol.2016.10.009","volume":"287","author":"E Guatteo","year":"2017","unstructured":"Guatteo E, Rizzo FR, Federici M, Cordella A, Ledonne A, Latini L, et al. Functional alterations of the dopaminergic and glutamatergic systems in spontaneous \u03b1-synuclein overexpressing rats. Exp Neurol. 2017;287:21\u201333.","journal-title":"Exp Neurol"},{"key":"3588_CR26","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1038\/nn.4152","volume":"18","author":"ZB Rosen","year":"2015","unstructured":"Rosen ZB, Cheung S, Siegelbaum SA. Midbrain dopamine neurons bidirectionally regulate CA3-CA1 synaptic drive. Nat Neurosci. 2015;18:1763\u201371.","journal-title":"Nat Neurosci"},{"key":"3588_CR27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/ejn.13364","volume":"45","author":"P Krashia","year":"2017","unstructured":"Krashia P, Martini A, Nobili A, Aversa D, D\u2019Amelio M, Berretta N, et al. On the properties of identified dopaminergic neurons in the mouse substantia nigra and ventral tegmental area. Eur J Neurosci. 2017;45:92\u2013105.","journal-title":"Eur J Neurosci"},{"key":"3588_CR28","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/0006-8993(94)90512-6","volume":"668","author":"A Gasbarri","year":"1994","unstructured":"Gasbarri A, Verney C, Innocenzi R, Campana E, Pacitti C. Mesolimbic dopaminergic neurons innervating the hippocampal formation in the rat: a combined retrograde tracing and immunohistochemical study. Brain Res. 1994;668:71\u201379.","journal-title":"Brain Res"},{"key":"3588_CR29","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.tins.2017.05.005","volume":"40","author":"CG McNamara","year":"2017","unstructured":"McNamara CG, Dupret D. Two sources of dopamine for the hippocampus. Trends Neurosci. 2017;40:383\u20134.","journal-title":"Trends Neurosci"},{"key":"3588_CR30","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.neuron.2005.05.002","volume":"46","author":"JE Lisman","year":"2005","unstructured":"Lisman JE, Grace AA. The Hippocampal-VTA Loop: controlling the entry of information into long-term memory. Neuron. 2005;46:703\u201313.","journal-title":"Neuron"},{"key":"3588_CR31","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1126\/science.274.5284.99","volume":"274","author":"K Hsiao","year":"1996","unstructured":"Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996;274:99\u2013102.","journal-title":"Science"},{"key":"3588_CR32","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0306-4522(97)00093-6","volume":"80","author":"CD Richards","year":"1997","unstructured":"Richards CD, Shiroyama T, Kitai ST. Electrophysiological and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat. Neuroscience. 1997;80:545\u201357.","journal-title":"Neuroscience"},{"key":"3588_CR33","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1113\/jphysiol.1991.sp018571","volume":"436","author":"WH Yung","year":"1991","unstructured":"Yung WH, H\u00e4usser MA, Jack JJ. Electrophysiology of dopaminergic and non-dopaminergic neurones of the guinea-pig substantia nigra pars compacta in vitro. J Physiol. 1991;436:643\u201367.","journal-title":"J Physiol"},{"key":"3588_CR34","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1126\/science.7433992","volume":"210","author":"AA Grace","year":"1980","unstructured":"Grace AA, Bunney BS. Nigral dopamine neurons: intracellular recording and identification with L-Dopa injection and histofluorescence. Science. 1980;210:654\u20136.","journal-title":"Science"},{"key":"3588_CR35","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1093\/brain\/aws101","volume":"135","author":"C Costa","year":"2012","unstructured":"Costa C, Sgobio C, Siliquini S, Tozzi A, Tantucci M, Ghiglieri V, et al. Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson\u2019s disease. Brain J Neurol. 2012;135:1884\u201399.","journal-title":"Brain J Neurol"},{"key":"3588_CR36","doi-asserted-by":"publisher","first-page":"101884","DOI":"10.1016\/j.jchemneu.2020.101884","volume":"111","author":"S Esmaeili-Mahani","year":"2021","unstructured":"Esmaeili-Mahani S, Haghparast E, Nezhadi A, Abbasnejad M, Sheibani V. Apelin-13 prevents hippocampal synaptic plasticity impairment in Parkinsonism rats. J Chem Neuroanat. 2021;111:101884.","journal-title":"J Chem Neuroanat"},{"key":"3588_CR37","doi-asserted-by":"publisher","first-page":"7723","DOI":"10.1523\/JNEUROSCI.1454-06.2006","volume":"26","author":"N Lemon","year":"2006","unstructured":"Lemon N, Manahan-Vaughan D. Dopamine D1\/D5 receptors gate the acquisition of novel information through hippocampal long-term potentiation and long-term depression. J Neurosci Off J Soc Neurosci. 2006;26:7723\u20139.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"3588_CR38","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1126\/science.8389057","volume":"260","author":"U Frey","year":"1993","unstructured":"Frey U, Huang YY, Kandel ER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science. 1993;260:1661\u20134.","journal-title":"Science"},{"key":"3588_CR39","doi-asserted-by":"publisher","first-page":"RP100822","DOI":"10.7554\/eLife.100822","volume":"13","author":"T Fuchsberger","year":"2025","unstructured":"Fuchsberger T, Stockwell I, Woods M, Brzosko Z, Greger IH, Paulsen O. Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP. eLife. 2025;13:RP100822.","journal-title":"eLife"},{"key":"3588_CR40","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1007\/s00213-023-06448-x","volume":"240","author":"MO Chohan","year":"2023","unstructured":"Chohan MO, Fein H, Mirro S, O\u2019Reilly KC, Veenstra-VanderWeele J. Repeated chemogenetic activation of dopaminergic neurons induces reversible changes in baseline and amphetamine-induced behaviors. Psychopharmacology (Berl). 2023;240:2545\u201360.","journal-title":"Psychopharmacology (Berl)"},{"key":"3588_CR41","doi-asserted-by":"publisher","first-page":"2374","DOI":"10.1016\/j.celrep.2020.01.084","volume":"30","author":"C Salesse","year":"2020","unstructured":"Salesse C, Charest J, Doucet-Beaupr\u00e9 H, Castonguay A-M, Labrecque S, De Koninck P, et al. Opposite control of excitatory and inhibitory synapse formation by Slitrk2 and Slitrk5 on dopamine neurons modulates hyperactivity behavior. Cell Rep. 2020;30:2374\u20132386.e5.","journal-title":"Cell Rep"},{"key":"3588_CR42","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s40478-019-0814-3","volume":"7","author":"T Torre-Muruzabal","year":"2019","unstructured":"Torre-Muruzabal T, Devoght J, Van den Haute C, Br\u00f4ne B, Van der Perren A, Baekelandt V. Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an \u03b1-synuclein based rat model for Parkinson\u2019s disease. Acta Neuropathol Commun. 2019;7:160.","journal-title":"Acta Neuropathol Commun"},{"key":"3588_CR43","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1126\/science.1168878","volume":"324","author":"H-C Tsai","year":"2009","unstructured":"Tsai H-C, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, et al. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009;324:1080\u20134.","journal-title":"Science"},{"key":"3588_CR44","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/j.neuropharm.2007.02.010","volume":"52","author":"S Navakkode","year":"2007","unstructured":"Navakkode S, Sajikumar S, Frey JU. Synergistic requirements for the induction of dopaminergic D1\/D5-receptor-mediated LTP in hippocampal slices of rat CA1 in vitro. Neuropharmacology. 2007;52:1547\u201354.","journal-title":"Neuropharmacology"},{"key":"3588_CR45","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1101\/lm.1991910","volume":"17","author":"S Navakkode","year":"2010","unstructured":"Navakkode S, Sajikumar S, Sacktor TC, Frey JU. Protein kinase M\u03b6 is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites. Learn Mem. 2010;17:605\u201311.","journal-title":"Learn Mem"},{"key":"3588_CR46","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s00401-011-0825-z","volume":"121","author":"H Braak","year":"2011","unstructured":"Braak H, Del Tredici K. Alzheimer\u2019s pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol (Berl). 2011;121:589\u201395.","journal-title":"Acta Neuropathol (Berl)"},{"key":"3588_CR47","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70:960\u20139.","journal-title":"J Neuropathol Exp Neurol"},{"key":"3588_CR48","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40478-017-0411-2","volume":"5","author":"SC Kelly","year":"2017","unstructured":"Kelly SC, He B, Perez SE, Ginsberg SD, Mufson EJ, Counts SE. Locus coeruleus cellular and molecular pathology during the progression of Alzheimer\u2019s disease. Acta Neuropathol Commun. 2017;5:8.","journal-title":"Acta Neuropathol Commun"},{"key":"3588_CR49","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj2511","volume":"13","author":"HIL Jacobs","year":"2021","unstructured":"Jacobs HIL, Becker JA, Kwong K, Engels-Dom\u00ednguez N, Prokopiou PC, Papp KV, et al. In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer\u2019s disease pathology and cognitive decline. Sci Transl Med. 2021;13:eabj2511.","journal-title":"Sci Transl Med"},{"key":"3588_CR50","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.neurobiolaging.2014.10.041","volume":"36","author":"HIL Jacobs","year":"2015","unstructured":"Jacobs HIL, Wiese S, van de Ven V, Gronenschild EHBM, Verhey FRJ, Matthews PM. Relevance of parahippocampal-locus coeruleus connectivity to memory in early dementia. Neurobiol Aging. 2015;36:618\u201326.","journal-title":"Neurobiol Aging"},{"key":"3588_CR51","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0022-510X(86)90179-6","volume":"76","author":"B Marcyniuk","year":"1986","unstructured":"Marcyniuk B, Mann DM, Yates PO. The topography of cell loss from locus caeruleus in Alzheimer\u2019s disease. J Neurol Sci. 1986;76:335\u201345.","journal-title":"J Neurol Sci"},{"key":"3588_CR52","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1073\/pnas.0909586107","volume":"107","author":"MT Heneka","year":"2010","unstructured":"Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, et al. Locus ceruleus controls Alzheimer\u2019s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci USA. 2010;107:6058\u201363.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3588_CR53","doi-asserted-by":"publisher","first-page":"13805","DOI":"10.1523\/JNEUROSCI.4218-08.2008","volume":"28","author":"Y Liu","year":"2008","unstructured":"Liu Y, Yoo M-J, Savonenko A, Stirling W, Price DL, Borchelt DR, et al. Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer\u2019s disease. J Neurosci Off J Soc Neurosci. 2008;28:13805\u201314.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"3588_CR54","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3233\/JAD-180094","volume":"63","author":"M D\u2019Amelio","year":"2018","unstructured":"D\u2019Amelio M, Serra L, Bozzali M. Ventral tegmental area in prodromal Alzheimer\u2019s Disease: bridging the gap between mice and humans. J Alzheimers Dis JAD. 2018;63:181\u20133.","journal-title":"J Alzheimers Dis JAD"},{"key":"3588_CR55","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3233\/JAD-171018","volume":"63","author":"M De Marco","year":"2018","unstructured":"De Marco M, Venneri A. Volume and connectivity of the ventral tegmental area are linked to neurocognitive signatures of Alzheimer\u2019s disease in humans. J Alzheimers Dis JAD. 2018;63:167\u201380.","journal-title":"J Alzheimers Dis JAD"},{"key":"3588_CR56","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.3233\/JAD-190954","volume":"75","author":"L Iaccarino","year":"2020","unstructured":"Iaccarino L, Sala A, Caminiti SP, Presotto L, Perani D, Alzheimer\u2019s Disease Neuroimaging Initiative. In vivo MRI structural and PET metabolic connectivity study of dopamine pathways in Alzheimer\u2019s disease. J Alzheimers Dis JAD. 2020;75:1003\u201316.","journal-title":"J Alzheimers Dis JAD"},{"key":"3588_CR57","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3389\/fnmol.2019.00123","volume":"12","author":"P Krashia","year":"2019","unstructured":"Krashia P, Nobili A, D\u2019Amelio M. Unifying hypothesis of dopamine neuron loss in neurodegenerative diseases: focusing on Alzheimer\u2019s disease. Front Mol Neurosci. 2019;12:123.","journal-title":"Front Mol Neurosci"},{"key":"3588_CR58","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00406-022-01417-5","volume":"273","author":"R Manca","year":"2023","unstructured":"Manca R, Valera-Bermejo JM, Venneri A, Alzheimer\u2019s disease Neuroimaging Initiative. Accelerated atrophy in dopaminergic targets and medial temporo-parietal regions precedes the onset of delusions in patients with Alzheimer\u2019s disease. Eur Arch Psychiatry Clin Neurosci. 2023;273:229\u201341.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"3588_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101907","volume":"87","author":"E Possemato","year":"2023","unstructured":"Possemato E, La Barbera L, Nobili A, Krashia P, D\u2019Amelio M. The role of dopamine in NLRP3 inflammasome inhibition: Implications for neurodegenerative diseases. Ageing Res Rev. 2023;87:101907.","journal-title":"Ageing Res Rev"},{"key":"3588_CR60","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s13195-021-00925-1","volume":"13","author":"A Sala","year":"2021","unstructured":"Sala A, Caminiti SP, Presotto L, Pilotto A, Liguori C, Chiaravalloti A, et al. In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer\u2019s disease phases. Alzheimers Res Ther. 2021;13:187.","journal-title":"Alzheimers Res Ther"},{"key":"3588_CR61","doi-asserted-by":"publisher","first-page":"985","DOI":"10.3233\/JAD-210171","volume":"82","author":"L Serra","year":"2021","unstructured":"Serra L, D\u2019Amelio M, Esposito S, Di Domenico C, Koch G, Marra C, et al. Ventral tegmental area disconnection contributes two years early to correctly classify patients converted to Alzheimer\u2019s disease: implications for treatment. J Alzheimers Dis JAD. 2021;82:985\u20131000.","journal-title":"J Alzheimers Dis JAD"},{"key":"3588_CR62","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.neurobiolaging.2018.08.012","volume":"72","author":"L Serra","year":"2018","unstructured":"Serra L, D\u2019Amelio M, Di Domenico C, Dipasquale O, Marra C, Mercuri NB, et al. In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer\u2019s disease. Neurobiol Aging. 2018;72:72\u201382.","journal-title":"Neurobiol Aging"},{"key":"3588_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71368-1","volume":"10","author":"A Venneri","year":"2020","unstructured":"Venneri A, De Marco M. Reduced monoaminergic nuclei MRI signal detectable in pre-symptomatic older adults with future memory decline. Sci Rep. 2020;10:18707.","journal-title":"Sci Rep"},{"key":"3588_CR64","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf008","volume":"7","author":"R Manca","year":"2025","unstructured":"Manca R, De Marco M, Soininen H, Ruffini L, Venneri A. Changes in neurotransmitter-related functional connectivity along the Alzheimer\u2019s disease continuum. Brain Commun. 2025;7:fcaf008.","journal-title":"Brain Commun"},{"key":"3588_CR65","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1038\/s41380-025-02913-5","volume":"30","author":"A Pilotto","year":"2025","unstructured":"Pilotto A, Galli A, Sala A, Caminiti SP, Presotto L, Liguori C. et al. Dopaminergic deficits along the spectrum of Alzheimeras disease. Mol Psychiatry. 2025;30:3069\u20133076.","journal-title":"Mol Psychiatry"},{"key":"3588_CR66","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.4103\/NRR.NRR-D-24-00230","volume":"20","author":"Y Zhang","year":"2025","unstructured":"Zhang Y, Liang Y, Gu Y. The dopaminergic system and Alzheimer\u2019s disease. Neural Regen Res. 2025;20:2495\u2013512.","journal-title":"Neural Regen Res"},{"key":"3588_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.782786","volume":"15","author":"J Brougher","year":"2021","unstructured":"Brougher J, Aziz U, Adari N, Chaturvedi M, Jules A, Shah I, et al. Self-Administration of Right Vagus Nerve Stimulation Activates Midbrain Dopaminergic Nuclei. Front Neurosci. 2021;15:782786.","journal-title":"Front Neurosci"},{"key":"3588_CR68","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.brs.2017.03.012","volume":"10","author":"T Peanlikhit","year":"2017","unstructured":"Peanlikhit T, Van Waes V, Pedron S, Risold P-Y, Haffen E, Eti\u00e9vant A, et al. The antidepressant-like effect of tDCS in mice: a behavioral and neurobiological characterization. Brain Stimulat. 2017;10:748\u201356.","journal-title":"Brain Stimulat"},{"key":"3588_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.44","volume":"3","author":"VS Chib","year":"2013","unstructured":"Chib VS, Yun K, Takahashi H, Shimojo S. Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex. Transl Psychiatry. 2013;3:e268.","journal-title":"Transl Psychiatry"},{"key":"3588_CR70","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s40035-024-00423-y","volume":"13","author":"ML De Paolis","year":"2024","unstructured":"De Paolis ML, Paoletti I, Zaccone C, Capone F, D\u2019Amelio M, Krashia P. Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer\u2019s disease. Transl Neurodegener. 2024;13:33.","journal-title":"Transl Neurodegener"},{"key":"3588_CR71","doi-asserted-by":"publisher","first-page":"e43","DOI":"10.1093\/brain\/awad019","volume":"146","author":"M D\u2019Amelio","year":"2023","unstructured":"D\u2019Amelio M, Di Lazzaro V. Can transcranial magnetic stimulation rescue dopaminergic signalling in Alzheimer\u2019s disease? Brain J Neurol. 2023;146:e43\u2013e45.","journal-title":"Brain J Neurol"},{"key":"3588_CR72","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13195-025-01736-4","volume":"17","author":"ML De Paolis","year":"2025","unstructured":"De Paolis ML, Loffredo G, Krashia P, La Barbera L, Nobili A, Cauzzi E, et al. Repetitive prefrontal tDCS activates VTA dopaminergic neurons, resulting in attenuation of Alzheimer\u2019s Disease-like deficits in Tg2576 mice. Alzheimers Res Ther. 2025;17:94.","journal-title":"Alzheimers Res Ther"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03588-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03588-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03588-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T08:03:32Z","timestamp":1759737812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03588-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3588"],"URL":"https:\/\/doi.org\/10.1038\/s41398-025-03588-w","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]},"assertion":[{"value":"25 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"371"}}