{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:05:19Z","timestamp":1784005519742,"version":"3.55.0"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Compulsive drug use despite negative consequences is a core addiction feature and key therapeutic target. Animal models utilize footshock to screen for mice exhibiting compulsive-like addiction traits. Following the administration of aversive stimuli, compulsive animals persist in drug-seeking, suggesting that addicted individuals may have impaired innate defensive responses, thereby exacerbating addictive behaviors. However, little is known about the neural mechanisms behind this behavior. The superior colliculus (SC), a multisensory integration hub, plays a crucial regulatory role in innate fear and defense. This study employed an optical intracranial self-stimulation (oICSS) addiction-like model. Using footshock to screen for mice with compulsive-like behavior, fiber photometry recordings revealed significant differences in neuronal activity within the SC. Specifically, SC neurons in compulsive-like mice showed significantly lower responses to footshock stimuli compared to non-compulsive mice. Subsequently, chemogenetic inhibition of SC neuronal activity in non-compulsive mice significantly reduced their resistance to footshock, inducing a compulsive-like state. Conversely, chemogenetic activation of SC neurons in compulsive-like mice significantly decreased their oICSS behavior. These findings indicate that mice exhibiting compulsive-like addiction behavior, identified through footshock, exhibit significant functional abnormalities in SC neurons. The SC is implicated in regulating compulsive addictive behaviors, providing novel insights into the mechanisms of compulsivity and identifying a promising new target for addiction intervention.<\/jats:p>","DOI":"10.1038\/s41398-026-04103-5","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:16:54Z","timestamp":1779347814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Superior colliculus modulates the compulsion in a model of addiction with foot-shock"],"prefix":"10.1038","volume":"16","author":[{"given":"Meng-Die","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-3589","authenticated-orcid":false,"given":"Jian-Guo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4781-8673","authenticated-orcid":false,"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hong","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-2057","authenticated-orcid":false,"given":"Rui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"4103_CR1","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1126\/science.1098975","volume":"305","author":"LJMJ Vanderschuren","year":"2004","unstructured":"Vanderschuren LJMJ, Everitt BJ. Drug seeking becomes compulsive after prolonged cocaine self-administration. Science. 2004;305:1017\u20139.","journal-title":"Science"},{"key":"4103_CR2","unstructured":"Diagnostic and statistical manual of mental disorders: DSM-5TM, 5th ed. https:\/\/psycnet.apa.org\/record\/2013-14907-000. Accessed 27 June2025."},{"key":"4103_CR3","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41586-018-0789-4","volume":"564","author":"V Pascoli","year":"2018","unstructured":"Pascoli V, Hiver A, Van Zessen R, Loureiro M, Achargui R, Harada M, et al. Stochastic synaptic plasticity underlying compulsion in a model of addiction. Nature. 2018;564:366\u201371.","journal-title":"Nature"},{"key":"4103_CR4","doi-asserted-by":"publisher","first-page":"9066","DOI":"10.1073\/pnas.1819978116","volume":"116","author":"Y Hu","year":"2019","unstructured":"Hu Y, Salmeron BJ, Krasnova IN, Gu H, Lu H, Bonci A, et al. Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals. Proc Natl Acad Sci USA. 2019;116:9066\u201371.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4103_CR5","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1126\/science.abi9086","volume":"373","author":"Y Li","year":"2021","unstructured":"Li Y, Simmler LD, Van Zessen R, Flakowski J, Wan J-X, Deng F, et al. Synaptic mechanism underlying serotonin modulation of transition to cocaine addiction. Science. 2021;373:1252\u20136.","journal-title":"Science"},{"key":"4103_CR6","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq5745","volume":"8","author":"Y Chen","year":"2022","unstructured":"Chen Y, Wang G, Zhang W, Han Y, Zhang L, Xu H, et al. An orbitofrontal cortex\u2013anterior insular cortex circuit gates compulsive cocaine use. Sci Adv. 2022;8:eabq5745.","journal-title":"Sci Adv"},{"key":"4103_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46460-z","volume":"15","author":"A Ritter","year":"2024","unstructured":"Ritter A, Habusha S, Givon L, Edut S, Klavir O. Prefrontal control of superior colliculus modulates innate escape behavior following adversity. Nat Commun. 2024;15:2158.","journal-title":"Nat Commun"},{"key":"4103_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7756","volume":"6","author":"P Wei","year":"2015","unstructured":"Wei P, Liu N, Zhang Z, Liu X, Tang Y, He X, et al. Processing of visually evoked innate fear by a non-canonical thalamic pathway. Nat Commun. 2015;6:6756.","journal-title":"Nat Commun"},{"key":"4103_CR9","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.cub.2018.12.031","volume":"29","author":"Z Zhang","year":"2019","unstructured":"Zhang Z, Liu W-Y, Diao Y-P, Xu W, Zhong Y-H, Zhang J-Y, et al. Superior colliculus GABAergic neurons are essential for acute dark induction of wakefulness in mice. Curr Biol: CB. 2019;29:637\u201344.e3.","journal-title":"Curr Biol: CB"},{"key":"4103_CR10","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1007\/s12264-022-00858-1","volume":"38","author":"X Liu","year":"2022","unstructured":"Liu X, Huang H, Snutch TP, Cao P, Wang L, Wang F. The superior colliculus: cell types, connectivity, and behavior. Neurosci Bull. 2022;38:1519\u201340.","journal-title":"Neurosci Bull"},{"key":"4103_CR11","doi-asserted-by":"crossref","unstructured":"May PJ. The mammalian superior colliculus: laminar structure and connections. In: Progress in brain research. Elsevier, 2006, pp 321\u201378.","DOI":"10.1016\/S0079-6123(05)51011-2"},{"key":"4103_CR12","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1126\/science.177.4047.444","volume":"177","author":"VA Casagrande","year":"1972","unstructured":"Casagrande VA, Harting JK, Hall WC, Diamond IT, Martin GF. Superior colliculus of the tree shrew: a structural and functional subdivision into superficial and deep layers. Science. 1972;177:444\u20137.","journal-title":"Science"},{"key":"4103_CR13","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/0166-2236(89)90052-0","volume":"12","author":"P Dean","year":"1989","unstructured":"Dean P, Redgrave P, Westby GWM. Event or emergency? two response systems in the mammalian superior colliculus. Trends Neurosci. 1989;12:137\u201347.","journal-title":"Trends Neurosci"},{"key":"4103_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03580-7","volume":"9","author":"C Shang","year":"2018","unstructured":"Shang C, Chen Z, Liu A, Li Y, Zhang J, Qu B, et al. Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice. Nat Commun. 2018;9:1232.","journal-title":"Nat Commun"},{"key":"4103_CR15","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1152\/jn.1998.80.2.1006","volume":"80","author":"MT Wallace","year":"1998","unstructured":"Wallace MT, Meredith MA, Stein BE. Multisensory integration in the superior colliculus of the alert cat. J Neurophysiol. 1998;80:1006\u201310.","journal-title":"J Neurophysiol"},{"key":"4103_CR16","doi-asserted-by":"publisher","first-page":"4564","DOI":"10.1016\/j.cell.2021.07.002","volume":"184","author":"MJ Ferreira-Pinto","year":"2021","unstructured":"Ferreira-Pinto MJ, Kanodia H, Falasconi A, Sigrist M, Esposito MS, Arber S. Functional diversity for body actions in the mesencephalic locomotor region. Cell. 2021;184:4564\u201378.e18.","journal-title":"Cell"},{"key":"4103_CR17","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41586-018-0244-6","volume":"558","author":"DA Evans","year":"2018","unstructured":"Evans DA, Stempel AV, Vale R, Ruehle S, Lefler Y, Branco T. A synaptic threshold mechanism for computing escape decisions. Nature. 2018;558:590\u20134.","journal-title":"Nature"},{"key":"4103_CR18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3389\/fnana.2012.00009","volume":"6","author":"E Comoli","year":"2012","unstructured":"Comoli E, Das Neves Favaro P, Vautrelle N, Leriche M, Overton PG, Redgrave P. Segregated anatomical input to sub-regions of the rodent superior colliculus associated with approach and defense. Front Neuroanat. 2012;6:9.","journal-title":"Front Neuroanat"},{"key":"4103_CR19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/BF00255241","volume":"68","author":"P Redgrave","year":"1987","unstructured":"Redgrave P, Mitchell IJ, Dean P. Descending projections from the superior colliculus in rat: a study using orthograde transport of wheatgerm-agglutinin conjugated horseradish peroxidase. Exp Brain Res. 1987;68:147\u201367.","journal-title":"Exp Brain Res"},{"key":"4103_CR20","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s00221-009-1880-8","volume":"198","author":"BE Stein","year":"2009","unstructured":"Stein BE, Stanford TR, Ramachandran R, Perrault TJ, Rowland BA. Challenges in quantifying multisensory integration: alternative criteria, models, and inverse effectiveness. Exp Brain Res. 2009;198:113\u201326.","journal-title":"Exp Brain Res"},{"key":"4103_CR21","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1152\/jn.1986.56.3.640","volume":"56","author":"MA Meredith","year":"1986","unstructured":"Meredith MA, Stein BE. Visual, auditory, and somatosensory convergence on cells in superior colliculus results in multisensory integration. J Neurophysiol. 1986;56:640\u201362.","journal-title":"J Neurophysiol"},{"key":"4103_CR22","doi-asserted-by":"publisher","first-page":"e60782","DOI":"10.1371\/journal.pone.0060782","volume":"8","author":"J Verhaal","year":"2013","unstructured":"Verhaal J, Luksch H. Mapping of the receptive fields in the optic tectum of chicken (gallus gallus) using sparse noise. PLOS One. 2013;8:e60782.","journal-title":"PLOS One"},{"key":"4103_CR23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50678","volume":"9","author":"KH Lee","year":"2020","unstructured":"Lee KH, Tran A, Turan Z, Meister M. The sifting of visual information in the superior colliculus. Elife. 2020;9:e50678.","journal-title":"Elife"},{"key":"4103_CR24","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nrn2331","volume":"9","author":"BE Stein","year":"2008","unstructured":"Stein BE, Stanford TR. Multisensory integration: current issues from the perspective of the single neuron. Nat Rev Neurosci. 2008;9:255\u201366.","journal-title":"Nat Rev Neurosci"},{"key":"4103_CR25","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1126\/science.3969558","volume":"227","author":"MA Meredith","year":"1985","unstructured":"Meredith MA, Stein BE. Descending efferents from the superior colliculus relay integrated multisensory information. Sci. 1985;227:657\u20139.","journal-title":"Sci"},{"key":"4103_CR26","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev-vision-102016-061234","volume":"3","author":"MA Basso","year":"2017","unstructured":"Basso MA, May PJ. Circuits for action and cognition: a view from the superior colliculus. Annu Rev Vis Sci. 2017;3:197\u2013226.","journal-title":"Annu Rev Vis Sci"},{"key":"4103_CR27","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1152\/jn.90275.2008","volume":"100","author":"M Isoda","year":"2008","unstructured":"Isoda M, Hikosaka O. A neural correlate of motivational conflict in the superior colliculus of the macaque. J Neurophysiol. 2008;100:1332\u201342.","journal-title":"J Neurophysiol"},{"key":"4103_CR28","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1152\/jn.2002.88.4.2019","volume":"88","author":"RM McPeek","year":"2002","unstructured":"McPeek RM, Keller EL. Saccade target selection in the superior colliculus during a visual search task. J Neurophysiol. 2002;88:2019\u201334.","journal-title":"J Neurophysiol"},{"key":"4103_CR29","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1146\/annurev-neuro-062012-170249","volume":"36","author":"RJ Krauzlis","year":"2013","unstructured":"Krauzlis RJ, Lovejoy LP, Z\u00e9non A. Superior colliculus and visual spatial attention. Annu Rev Neurosci. 2013;36:165\u201382.","journal-title":"Annu Rev Neurosci"},{"key":"4103_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2024.137997","volume":"842","author":"P-Y Li","year":"2024","unstructured":"Li P-Y, Jing M-Y, Cun X-F, Wu N, Li J, Song R. The neural circuit of superior colliculus to ventral tegmental area modulates visual cue associated with rewarding behavior in optical intracranial self-stimulation in mice. Neurosci Lett. 2024;842:137997.","journal-title":"Neurosci Lett"},{"key":"4103_CR31","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.neuroscience.2010.04.018","volume":"168","author":"KM Igelstrom","year":"2010","unstructured":"Igelstrom KM, Herbison AE, Hyland BI. Enhanced c-fos expression in superior colliculus, paraventricular thalamus and septum during learning of cue-reward association. Neuroscience. 2010;168:706\u201314.","journal-title":"Neuroscience"},{"key":"4103_CR32","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1007\/s12035-021-02597-2","volume":"59","author":"SN Awathale","year":"2022","unstructured":"Awathale SN, Waghade AM, Kawade HM, Jadhav G, Choudhary AG, Sagarkar S, et al. Neuroplastic changes in the superior colliculus and hippocampus in self-rewarding paradigm: importance of visual cues. Mol Neurobiol. 2022;59:890\u2013915.","journal-title":"Mol Neurobiol"},{"key":"4103_CR33","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwae467","volume":"12","author":"Y Liu","year":"2024","unstructured":"Liu Y, Zhou Z-X, Lv Q, Huang G, Zhang H, Wang Y-Q, et al. A superior colliculus-originating circuit prevents cocaine reinstatement via VR-based eye movement desensitization treatment. Natl Sci Rev. 2024;12:nwae467.","journal-title":"Natl Sci Rev"},{"key":"4103_CR34","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24459","volume":"6","author":"N Takakuwa","year":"2017","unstructured":"Takakuwa N, Kato R, Redgrave P, Isa T. Emergence of visually-evoked reward expectation signals in dopamine neurons via the superior colliculus in V1 lesioned monkeys. Elife. 2017;6:e24459.","journal-title":"Elife"},{"key":"4103_CR35","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1126\/science.1107026","volume":"307","author":"E Dommett","year":"2005","unstructured":"Dommett E, Coizet V, Blaha CD, Martindale J, Lefebvre V, Walton N, et al. How visual stimuli activate dopaminergic neurons at short latency. Sci. 2005;307:1476\u20139.","journal-title":"Sci"},{"key":"4103_CR36","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1038\/nrn2022","volume":"7","author":"P Redgrave","year":"2006","unstructured":"Redgrave P, Gurney K. The short-latency dopamine signal: a role in discovering novel actions?. Nat Rev Neurosci. 2006;7:967\u201375.","journal-title":"Nat Rev Neurosci"},{"key":"4103_CR37","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.neuron.2015.08.037","volume":"88","author":"R Keiflin","year":"2015","unstructured":"Keiflin R, Janak PH. Dopamine prediction errors in reward learning and addiction: from theory to neural circuitry. Neuron. 2015;88:247\u201363.","journal-title":"Neuron"},{"key":"4103_CR38","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.tins.2005.06.006","volume":"28","author":"JG McHaffie","year":"2005","unstructured":"McHaffie JG, Stanford TR, Stein BE, Coizet V, Redgrave P. Subcortical loops through the basal ganglia. Trends Neurosci. 2005;28:401\u20137.","journal-title":"Trends Neurosci"},{"key":"4103_CR39","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.neuron.2019.05.027","volume":"103","author":"Z Zhou","year":"2019","unstructured":"Zhou Z, Liu X, Chen S, Zhang Z, Liu Y, Montardy Q, et al. A VTA GABAergic neural circuit mediates visually evoked innate defensive responses. Neuron. 2019;103:473\u201388.e6.","journal-title":"Neuron"},{"key":"4103_CR40","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.neuroscience.2005.11.015","volume":"138","author":"JG McHaffie","year":"2006","unstructured":"McHaffie JG, Jiang H, May PJ, Coizet V, Overton PG, Stein BE, et al. A direct projection from superior colliculus to substantia nigra pars compacta in the cat. Neuroscience. 2006;138:221\u201334.","journal-title":"Neuroscience"},{"key":"4103_CR41","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.tins.2013.08.005","volume":"36","author":"A Reiner","year":"2013","unstructured":"Reiner A, Isacoff EY. The brain prize 2013: the optogenetics revolution. Trends Neurosci. 2013;36:557\u201360.","journal-title":"Trends Neurosci"},{"key":"4103_CR42","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3410\/B3-11","volume":"3","author":"ES Boyden","year":"2011","unstructured":"Boyden ES. A history of optogenetics: the development of tools for controlling brain circuits with light. F1000 Biol Rep. 2011;3:11.","journal-title":"F1000 Biol Rep"},{"key":"4103_CR43","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fncir.2013.00152","volume":"7","author":"J-H Baik","year":"2013","unstructured":"Baik J-H. Dopamine signaling in reward-related behaviors. Front Neural Circuits. 2013;7:152.","journal-title":"Front Neural Circuits"},{"key":"4103_CR44","doi-asserted-by":"publisher","first-page":"e437","DOI":"10.1371\/journal.pmed.0030437","volume":"3","author":"C L\u00fcscher","year":"2006","unstructured":"L\u00fcscher C, Ungless MA. The mechanistic classification of addictive drugs. PLoS Med. 2006;3:e437.","journal-title":"PLoS Med"},{"key":"4103_CR45","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.neuropharm.2004.06.032","volume":"47","author":"G Di Chiara","year":"2004","unstructured":"Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, et al. Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology. 2004;47:227\u201341.","journal-title":"Neuropharmacology"},{"key":"4103_CR46","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. Sci. 2009;324:1080\u20134.","journal-title":"Sci"},{"key":"4103_CR47","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s11011-017-0023-3","volume":"32","author":"X Han","year":"2017","unstructured":"Han X, Jing M-Y, Zhao T-Y, Wu N, Song R, Li J. Role of dopamine projections from ventral tegmental area to nucleus accumbens and medial prefrontal cortex in reinforcement behaviors assessed using optogenetic manipulation. Metab Brain Dis. 2017;32:1491\u2013502.","journal-title":"Metab Brain Dis"},{"key":"4103_CR48","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1038\/s41593-018-0191-4","volume":"21","author":"BT Saunders","year":"2018","unstructured":"Saunders BT, Richard JM, Margolis EB, Janak PH. Dopamine neurons create pavlovian conditioned stimuli with circuit-defined motivational properties. Nat Neurosci. 2018;21:1072\u201383.","journal-title":"Nat Neurosci"},{"key":"4103_CR49","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/j.neuron.2015.10.017","volume":"88","author":"V Pascoli","year":"2015","unstructured":"Pascoli V, Terrier J, Hiver A, L\u00fcscher C. Sufficiency of mesolimbic dopamine neuron stimulation for the progression to addiction. Neuron. 2015;88:1054\u201366.","journal-title":"Neuron"},{"key":"4103_CR50","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3389\/fnmol.2017.00284","volume":"10","author":"JR Deuis","year":"2017","unstructured":"Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci. 2017;10:284.","journal-title":"Front Mol Neurosci"},{"key":"4103_CR51","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1126\/science.aaa8694","volume":"348","author":"C Shang","year":"2015","unstructured":"Shang C, Liu Z, Chen Z, Shi Y, Wang Q, Liu S, et al. BRAIN CIRCUITS. A parvalbumin-positive excitatory visual pathway to trigger fear responses in mice. Sci. 2015;348:1472\u20137.","journal-title":"Sci"},{"key":"4103_CR52","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.neuron.2011.01.017","volume":"69","author":"C L\u00fcscher","year":"2011","unstructured":"L\u00fcscher C, Malenka RC. Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron. 2011;69:650\u201363.","journal-title":"Neuron"},{"key":"4103_CR53","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41583-024-00807-z","volume":"25","author":"TW Robbins","year":"2024","unstructured":"Robbins TW, Banca P, Belin D. From compulsivity to compulsion: the neural basis of compulsive disorders. Nat Rev Neurosci. 2024;25:313\u201333.","journal-title":"Nat Rev Neurosci"},{"key":"4103_CR54","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.tips.2007.01.008","volume":"28","author":"PJ Kenny","year":"2007","unstructured":"Kenny PJ. Brain reward systems and compulsive drug use. Trends Pharmacol Sci. 2007;28:135\u201341.","journal-title":"Trends Pharmacol Sci"},{"key":"4103_CR55","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/s41583-020-0289-z","volume":"21","author":"C L\u00fcscher","year":"2020","unstructured":"L\u00fcscher C, Robbins TW, Everitt BJ. The transition to compulsion in addiction. Nat Rev Neurosci. 2020;21:247\u201363.","journal-title":"Nat Rev Neurosci"},{"key":"4103_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48577-7","volume":"15","author":"D Han","year":"2024","unstructured":"Han D, Doya K, Li D, Tani J. Synergizing habits and goals with variational Bayes. Nat Commun. 2024;15:4461.","journal-title":"Nat Commun"},{"key":"4103_CR57","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.pharmthera.2005.06.018","volume":"108","author":"CP O\u2019Brien","year":"2005","unstructured":"O\u2019Brien CP, Gardner EL. Critical assessment of how to study addiction and its treatment: Human and non-human animal models. Pharmacol Ther. 2005;108:18\u201358.","journal-title":"Pharmacol Ther"},{"key":"4103_CR58","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1126\/science.1099020","volume":"305","author":"V Deroche-Gamonet","year":"2004","unstructured":"Deroche-Gamonet V, Belin D, Piazza PV. Evidence for addiction-like behavior in the rat. Science. 2004;305:1014\u20137.","journal-title":"Science"},{"key":"4103_CR59","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1016\/j.pnpbp.2007.08.028","volume":"31","author":"DCS Roberts","year":"2007","unstructured":"Roberts DCS, Morgan D, Liu Y. How to make a rat addicted to cocaine. Prog Neuro-psychopharmacol Biol Psychiatry. 2007;31:1614\u201324.","journal-title":"Prog Neuro-psychopharmacol Biol Psychiatry"},{"key":"4103_CR60","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.biopsych.2015.01.004","volume":"79","author":"A Belin-Rauscent","year":"2016","unstructured":"Belin-Rauscent A, Fouyssac M, Bonci A, Belin D. How preclinical models evolved to resemble the diagnostic criteria of drug addiction. Biol Psychiatry. 2016;79:39\u201346.","journal-title":"Biol Psychiatry"},{"key":"4103_CR61","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.bbr.2017.03.009","volume":"326","author":"OV Torres","year":"2017","unstructured":"Torres OV, Jayanthi S, Ladenheim B, McCoy MT, Krasnova IN, Cadet JL. Compulsive methamphetamine taking under punishment is associated with greater cue-induced drug seeking in rats. Behav Brain Res. 2017;326:265\u201371.","journal-title":"Behav Brain Res"},{"key":"4103_CR62","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.neuron.2021.01.013","volume":"109","author":"MA Basso","year":"2021","unstructured":"Basso MA, Bickford ME, Cang J. Unraveling circuits of visual perception and cognition through the superior colliculus. Neuron. 2021;109:918\u201337.","journal-title":"Neuron"},{"key":"4103_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.120322","volume":"280","author":"NG Prabhu","year":"2023","unstructured":"Prabhu NG, Himmelbach M. Activity in the human superior colliculus associated with reaching for tactile targets. Neuroimage. 2023;280:120322.","journal-title":"Neuroimage"},{"key":"4103_CR64","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.bbr.2009.05.033","volume":"204","author":"J De Ross","year":"2009","unstructured":"De Ross J, Avila MAV, Ruggiero RN, Nobre MJ, Brand\u00e3o ML, Castilho VM. The unconditioned fear produced by morphine withdrawal is regulated by mu- and kappa-opioid receptors in the midbrain tectum. Behav Brain Res. 2009;204:140\u20136.","journal-title":"Behav Brain Res"},{"key":"4103_CR65","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/j.addbeh.2014.01.002","volume":"39","author":"MJ Gullo","year":"2014","unstructured":"Gullo MJ, Loxton NJ, Dawe S. Impulsivity: four ways five factors are not basic to addiction. Addict Behav. 2014;39:1547\u201356.","journal-title":"Addict Behav"},{"key":"4103_CR66","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1177\/0956797611400615","volume":"22","author":"RW Wiers","year":"2011","unstructured":"Wiers RW, Eberl C, Rinck M, Becker ES, Lindenmeyer J. Retraining automatic action tendencies changes alcoholic patients\u2019 approach bias for alcohol and improves treatment outcome. Psychol Sci. 2011;22:490\u20137.","journal-title":"Psychol Sci"},{"key":"4103_CR67","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1111\/j.1460-9568.2012.08217.x","volume":"36","author":"BT Saunders","year":"2012","unstructured":"Saunders BT, Robinson TE. The role of dopamine in the accumbens core in the expression of Pavlovian-conditioned responses. Eur J Neurosci. 2012;36:2521\u201332. https:\/\/doi.org\/10.1111\/j.1460-9568.2012.08217.x.","journal-title":"Eur J Neurosci"},{"key":"4103_CR68","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/nrn2234","volume":"8","author":"JA Kauer","year":"2007","unstructured":"Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat Rev Neurosci. 2007;8:844\u201358. https:\/\/doi.org\/10.1038\/nrn2234.","journal-title":"Nat Rev Neurosci"},{"key":"4103_CR69","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1098\/rstb.2002.1236","volume":"358","author":"MJ Thomas","year":"2003","unstructured":"Thomas MJ, Malenka RC. Synaptic plasticity in the mesolimbic dopamine system. Phil Trans R Soc Lond B. 2003;358:815\u20139.","journal-title":"Phil Trans R Soc Lond B"},{"key":"4103_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-19192-3","volume":"15","author":"X Cun","year":"2025","unstructured":"Cun X, Zhu H, Wu N, Jing M, Song R. Superior colliculus encodes the visual cue associated with rewarding behavior in sucrose self-administration in mice. Sci Rep. 2025;15:35171.","journal-title":"Sci Rep"},{"key":"4103_CR71","doi-asserted-by":"publisher","first-page":"8663","DOI":"10.1523\/JNEUROSCI.0089-23.2023","volume":"43","author":"LJ Baruchin","year":"2023","unstructured":"Baruchin LJ, Alleman M, Schr\u00f6der S. Reward modulates visual responses in the superficial superior colliculus of mice. J Neurosci. 2023;43:8663\u201380.","journal-title":"J Neurosci"},{"key":"4103_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14263","volume":"8","author":"BJ White","year":"2017","unstructured":"White BJ, Berg DJ, Kan JY, Marino RA, Itti L, Munoz DP. Superior colliculus neurons encode a visual saliency map during free viewing of natural dynamic video. Nat Commun. 2017;8:14263.","journal-title":"Nat Commun"},{"key":"4103_CR73","doi-asserted-by":"crossref","unstructured":"Haimerl C, Rodrigues FS, Paton JJ. Time, control, and the nervous system. Annual Review of Neuroscience. 2025;48:465\u201389.","DOI":"10.1146\/annurev-neuro-112723-025348"},{"key":"4103_CR74","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/nature11527","volume":"491","author":"S Lammel","year":"2012","unstructured":"Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, et al. Input-specific control of reward and aversion in the ventral tegmental area. Nature. 2012;491:212\u20137.","journal-title":"Nature"},{"key":"4103_CR75","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nature10754","volume":"482","author":"JY Cohen","year":"2012","unstructured":"Cohen JY, Haesler S, Vong L, Lowell BB, Uchida N. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature. 2012;482:85\u20138.","journal-title":"Nature"},{"key":"4103_CR76","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03125-y","volume":"9","author":"L Faget","year":"2018","unstructured":"Faget L, Zell V, Souter E, McPherson A, Ressler R, Gutierrez-Reed N, et al. Opponent control of behavioral reinforcement by inhibitory and excitatory projections from the ventral pallidum. Nat Commun. 2018;9:849.","journal-title":"Nat Commun"},{"key":"4103_CR77","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nature14855","volume":"525","author":"N Eshel","year":"2015","unstructured":"Eshel N, Bukwich M, Rao V, Hemmelder V, Tian J, Uchida N. Arithmetic and local circuitry underlying dopamine prediction errors. Nature. 2015;525:243\u20136.","journal-title":"Nature"},{"key":"4103_CR78","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.neuron.2020.01.012","volume":"106","author":"J Morrens","year":"2020","unstructured":"Morrens J, Aydin \u00c7, Janse van Rensburg A, Esquivelzeta Rabell J, Haesler S. Cue-evoked dopamine promotes conditioned responding during learning. Neuron. 2020;106:142\u201353.e7.","journal-title":"Neuron"},{"key":"4103_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01774-0","volume":"12","author":"S Mondoloni","year":"2022","unstructured":"Mondoloni S, Mameli M, Congiu M. Reward and aversion encoding in the lateral habenula for innate and learned behaviours. Transl Psychiatry. 2022;12:3.","journal-title":"Transl Psychiatry"},{"key":"4103_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49828-3","volume":"15","author":"C Demaestri","year":"2024","unstructured":"Demaestri C, Pisciotta M, Altunkeser N, Berry G, Hyland H, Breton J, et al. Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice. Nat Commun. 2024;15:5522.","journal-title":"Nat Commun"},{"key":"4103_CR81","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/s41582-024-00990-8","volume":"20","author":"FC Hummel","year":"2024","unstructured":"Hummel FC, Wessel MJ. Non-invasive deep brain stimulation: interventional targeting of deep brain areas in neurological disorders. Nat Rev Neurol. 2024;20:451\u20132.","journal-title":"Nat Rev Neurol"},{"key":"4103_CR82","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1227\/NEU.0b013e3182592faa","volume":"71","author":"JC Fernandez-Miranda","year":"2012","unstructured":"Fernandez-Miranda JC, Pathak S, Engh J, Jarbo K, Verstynen T, Yeh F-C, et al. High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications. Neurosurgery. 2012;71:430\u201353.","journal-title":"Neurosurgery"},{"key":"4103_CR83","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1007\/s00702-016-1541-6","volume":"123","author":"K Wietschorke","year":"2016","unstructured":"Wietschorke K, Lippold J, Jacob C, Polak T, Herrmann MJ. Transcranial direct current stimulation of the prefrontal cortex reduces cue-reactivity in alcohol-dependent patients. J Neural Transm. 2016;123:1173\u20138.","journal-title":"J Neural Transm"},{"key":"4103_CR84","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1001\/archgenpsychiatry.2010.46","volume":"67","author":"MS George","year":"2010","unstructured":"George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010;67:507\u201316.","journal-title":"Arch Gen Psychiatry"},{"key":"4103_CR85","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.clinph.2016.10.087","volume":"128","author":"J-P Lefaucheur","year":"2017","unstructured":"Lefaucheur J-P, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017;128:56\u201392.","journal-title":"Clin Neurophysiol"},{"key":"4103_CR86","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.brs.2009.08.002","volume":"2","author":"Y Levkovitz","year":"2009","unstructured":"Levkovitz Y, Harel EV, Roth Y, Braw Y, Most D, Katz LN, et al. Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients. Brain Stimul. 2009;2:188\u2013200.","journal-title":"Brain Stimul"},{"key":"4103_CR87","doi-asserted-by":"publisher","DOI":"10.1111\/adb.70057","volume":"30","author":"S Guldas","year":"2025","unstructured":"Guldas S, Tumkaya S, Yucens B. Deep transcranial magnetic stimulation in patients with opioid use disorder: a double-blind, placebo-controlled randomized trial. Addict Biol. 2025;30:e70057.","journal-title":"Addict Biol"},{"key":"4103_CR88","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114383","volume":"43","author":"J Lei","year":"2024","unstructured":"Lei J, Zhang P, Li T, Cui C, Li M, Yang X, et al. Alternating bilateral sensory stimulation alleviates alcohol-induced conditioned place preference via a superior colliculus-VTA circuit. Cell Rep. 2024;43:114383.","journal-title":"Cell Rep"},{"key":"4103_CR89","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/s41422-023-00920-1","volume":"34","author":"X Zhou","year":"2024","unstructured":"Zhou X, He Y, Xu T, Wu Z, Guo W, Xu X, et al. 40 Hz light flickering promotes sleep through cortical adenosine signaling. Cell Res. 2024;34:214\u201331.","journal-title":"Cell Res"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04103-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04103-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04103-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:25:48Z","timestamp":1784003148000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-04103-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4103"],"URL":"https:\/\/doi.org\/10.1038\/s41398-026-04103-5","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"assertion":[{"value":"14 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2026","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"}},{"value":"All animal procedures were approved by the Institutional Animal Care and Use Committee under permission No. IACUC-DWZX-2021-531 was performed strictly per the Guidelines for the Care and Use of Laboratory Animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statement"}}],"article-number":"359"}}