{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:18:49Z","timestamp":1784762329095,"version":"3.55.0"},"reference-count":52,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["948217"],"award-info":[{"award-number":["948217"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002943","name":"Departament d'Innovaci\u00f3, Universitats i Empresa, Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002943","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["SGR-00022"],"award-info":[{"award-number":["SGR-00022"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports Methods"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.crmeth.2025.101144","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:22:46Z","timestamp":1756394566000},"page":"101144","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Profiling mouse behavior with computational tools to assess age-dependent differences in associative learning"],"prefix":"10.1016","volume":"5","author":[{"given":"Marc","family":"Canela-Grimau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia S.","family":"Pinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Busquets-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.crmeth.2025.101144_bib1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/37601","article-title":"Fear conditioning induces associative long-term potentiation in the amygdala","volume":"390","author":"Rogan","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.crmeth.2025.101144_bib2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.neubiorev.2005.06.005","article-title":"Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review","volume":"30","author":"Kim","year":"2006","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.crmeth.2025.101144_bib3","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.neuron.2008.06.029","article-title":"Neural circuitry underlying the regulation of conditioned fear and its relation to extinction","volume":"59","author":"Delgado","year":"2008","journal-title":"Neuron"},{"key":"10.1016\/j.crmeth.2025.101144_bib4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1126\/science.1223252","article-title":"Preference by association: How memory mechanisms in the hippocampus bias decisions","volume":"338","author":"Wimmer","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.crmeth.2025.101144_bib5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1101\/lm.35200","article-title":"Using pavlovian higher-order conditioning paradigms to investigate the neural substrates of emotional learning and memory","volume":"7","author":"Gewirtz","year":"2000","journal-title":"Learn. Mem."},{"key":"10.1016\/j.crmeth.2025.101144_bib6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1515\/rns.2011.025","article-title":"Role of the basolateral amygdala and NMDA receptors in higher-order conditioned fear","volume":"22","author":"Parkes","year":"2011","journal-title":"revneuro"},{"key":"10.1016\/j.crmeth.2025.101144_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.neubiorev.2022.104687","article-title":"The neural substrates of higher-order conditioning: A review","volume":"138","author":"Holmes","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.crmeth.2025.101144_bib8","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2021.722796","article-title":"Neural substrates of incidental associations and mediated learning: The role of cannabinoid receptors","volume":"15","author":"Ioannidou","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib9","doi-asserted-by":"crossref","first-page":"10982","DOI":"10.1523\/JNEUROSCI.1349-14.2014","article-title":"Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning","volume":"34","author":"Robinson","year":"2014","journal-title":"J. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.neuron.2018.08.014","article-title":"Hippocampal CB1 receptors control incidental associations","volume":"99","author":"Busquets-Garcia","year":"2018","journal-title":"Neuron"},{"key":"10.1016\/j.crmeth.2025.101144_bib11","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-53977-w","article-title":"Parabrachial Calca neurons mediate second-order conditioning","volume":"15","author":"Park","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.crmeth.2025.101144_bib12","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2022.845616","article-title":"Understanding associative learning through higher-order conditioning","volume":"16","author":"Gostolupce","year":"2022","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib13","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2021.745388","article-title":"Higher-order conditioning and dopamine: Charting a path forward","volume":"15","author":"Seitz","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib14","series-title":"Associative Learning and Conditioning Theory","first-page":"481","article-title":"Effects of conditioning in advertising","author":"Schachtman","year":"2011"},{"key":"10.1016\/j.crmeth.2025.101144_bib15","series-title":"The Principles of Learning and Behavior","author":"Domjan","year":"2014"},{"key":"10.1016\/j.crmeth.2025.101144_bib16","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1037\/emo0000860","article-title":"Adult age-related differences in appetitive and aversive associative learning","volume":"21","author":"Freund","year":"2021","journal-title":"Emotion"},{"key":"10.1016\/j.crmeth.2025.101144_bib17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.physbeh.2009.02.035","article-title":"Sex differences in learning processes of classical and operant conditioning","volume":"97","author":"Dalla","year":"2009","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.crmeth.2025.101144_bib18","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1038\/s41386-020-0776-y","article-title":"Deep learning-based behavioral analysis reaches human accuracy and is capable of outperforming commercial solutions","volume":"45","author":"Sturman","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.crmeth.2025.101144_bib19","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/s41593-018-0209-y","article-title":"Deeplabcut: Markerless pose estimation of user-defined body parts with deep learning","volume":"21","author":"Mathis","year":"2018","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib20","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2022.1044492","article-title":"Using deep learning to study emotional behavior in rodent models","volume":"16","author":"Kuo","year":"2022","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib21","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/s41592-024-02318-2","article-title":"Keypoint-MoSeq: Parsing behavior by linking point tracking to pose dynamics","volume":"21","author":"Weinreb","year":"2024","journal-title":"Nat. Methods"},{"key":"10.1016\/j.crmeth.2025.101144_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-40040-3","article-title":"Automatically annotated motion tracking identifies a distinct social behavioral profile following chronic social defeat stress","volume":"14","author":"Bordes","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.crmeth.2025.101144_bib23","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-63458-1","article-title":"An ethologically relevant paradigm to assess defensive response to looming visual contrast stimuli","volume":"14","author":"Calanni","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.crmeth.2025.101144_bib24","article-title":"Catch me if you can: free-living mice show a highly flexible dodging behaviour suggestive of intentional tactical deception","volume":"11","author":"d\u2019Isa","year":"2024","journal-title":"R. Soc. Open Sci."},{"key":"10.1016\/j.crmeth.2025.101144_bib25","doi-asserted-by":"crossref","first-page":"12608","DOI":"10.1523\/JNEUROSCI.2949-10.2010","article-title":"The basolateral amygdala is critical for the acquisition and extinction of associations between a neutral stimulus and a learned danger signal but not between two neutral stimuli","volume":"30","author":"Parkes","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib26","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.0513-23.2023","article-title":"What is learned determines how pavlovian conditioned fear is consolidated in the brain","volume":"44","author":"Leake","year":"2024","journal-title":"J. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib27","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2015.00355","article-title":"Assessing fear following retrieval + extinction through suppression of baseline reward seeking vs. freezing","volume":"9","author":"Shumake","year":"2015","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib28","article-title":"Dorsal hippocampus mediates light-tone sensory preconditioning task in mice","author":"Pinho","year":"2025","journal-title":"bioRXiv"},{"key":"10.1016\/j.crmeth.2025.101144_bib29","first-page":"250","article-title":"Second-order conditioning in Drosophila. Learning amp","volume":"18","author":"Tabone","year":"2011","journal-title":"Memory"},{"key":"10.1016\/j.crmeth.2025.101144_bib30","doi-asserted-by":"crossref","first-page":"13112","DOI":"10.1523\/JNEUROSCI.1998-13.2013","article-title":"The basolateral amygdala is critical for learning about neutral stimuli in the presence of danger, and the perirhinal cortex is critical in the absence of danger","volume":"33","author":"Holmes","year":"2013","journal-title":"J. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib31","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2021.672628","article-title":"Second-Order conditioning in humans","volume":"15","author":"Lee","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2021.113435","article-title":"Mechanisms of higher-order learning in the amygdala","volume":"414","author":"Gostolupce","year":"2021","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.crmeth.2025.101144_bib33","first-page":"38","article-title":"Behavioral and neural mechanisms of latent inhibition. Learning amp","volume":"29","author":"Miller","year":"2022","journal-title":"Memory"},{"key":"10.1016\/j.crmeth.2025.101144_bib34","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1149027","article-title":"Open-source software for automated rodent behavioral analysis","volume":"17","author":"Isik","year":"2023","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib35","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0223-19.2019","article-title":"The future is open: Open-source tools for behavioral neuroscience research","volume":"6","author":"White","year":"2019","journal-title":"Eneuro"},{"key":"10.1016\/j.crmeth.2025.101144_bib36","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/s41593-024-01649-9","article-title":"Simple behavioral analysis (simba) as a platform for explainable machine learning in behavioral neuroscience","volume":"27","author":"Goodwin","year":"2024","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib37","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.74314","article-title":"Behaviordepot is a simple, flexible tool for automated behavioral detection based on markerless pose tracking","volume":"11","author":"Gabriel","year":"2022","journal-title":"eLife"},{"key":"10.1016\/j.crmeth.2025.101144_bib38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jneumeth.2008.12.021","article-title":"Automated scoring of fear-related behavior using ethovision software","volume":"178","author":"Pham","year":"2009","journal-title":"J. Neurosci. Methods"},{"key":"10.1016\/j.crmeth.2025.101144_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2024.1440601","article-title":"Comprehensive ethological analysis of fear expression in rats using deeplabcut and simba machine learning model","volume":"18","author":"Chanthongdee","year":"2024","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib40","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2023.1216524","article-title":"Update on neurobiological mechanisms of fear: Illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders","volume":"17","author":"Li","year":"2023","journal-title":"Front. Behav. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib41","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2017.07.013","article-title":"Distinct neural circuits for the formation and retrieval of episodic memories","volume":"170","author":"Roy","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.crmeth.2025.101144_bib42","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nature14030","article-title":"A temporal shift in the circuits mediating retrieval of fear memory","volume":"519","author":"Do-Monte","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.crmeth.2025.101144_bib43","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nature18630","article-title":"Prefrontal neuronal assemblies temporally control fear behaviour","volume":"535","author":"Dejean","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.crmeth.2025.101144_bib44","first-page":"943","article-title":"Comportement de peur: role des interneurones exprimant la parvalbumine du cortex pr\u00e9frontal m\u00e9dian","volume":"30","author":"Courtin","year":"2014","journal-title":"Med. Sci."},{"key":"10.1016\/j.crmeth.2025.101144_bib45","doi-asserted-by":"crossref","first-page":"7109","DOI":"10.1523\/JNEUROSCI.1054-12.2012","article-title":"Bimodal control of fear-coping strategies by cb1cannabinoid receptors","volume":"32","author":"Metna-Laurent","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib46","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.82497","article-title":"A fear conditioned cue orchestrates a suite of behaviors in rats","volume":"13","author":"Chu","year":"2024","journal-title":"eLife"},{"key":"10.1016\/j.crmeth.2025.101144_bib47","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1111\/ejn.14602","article-title":"The neurobiological basis of sex differences in learned fear and its inhibition","volume":"52","author":"Day","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2022.109298","article-title":"Sex differences in fear responses: Neural circuits","volume":"222","author":"Bauer","year":"2023","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.crmeth.2025.101144_bib49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1009867","article-title":"Measuring the repertoire of age-related behavioral changes in drosophila melanogaster","volume":"18","author":"Overman","year":"2022","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.crmeth.2025.101144_bib50","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1232670","article-title":"Age-related decline in cognitive flexibility is associated with the levels of hippocampal neurogenesis","volume":"17","author":"Amelchenko","year":"2023","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.crmeth.2025.101144_bib51","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-43142-0","article-title":"Functional alterations of the prefrontal circuit underlying cognitive aging in mice","volume":"14","author":"Chong","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.crmeth.2025.101144_bib52","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1038\/s41592-024-02500-6","article-title":"Analysis of behavioral flow resolves latent phenotypes","volume":"21","author":"von Ziegler","year":"2024","journal-title":"Nat. Methods"}],"container-title":["Cell Reports Methods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667237525001808?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2667237525001808?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T04:27:40Z","timestamp":1758688060000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2667237525001808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":52,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S2667237525001808"],"URL":"https:\/\/doi.org\/10.1016\/j.crmeth.2025.101144","relation":{},"ISSN":["2667-2375"],"issn-type":[{"value":"2667-2375","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Profiling mouse behavior with computational tools to assess age-dependent differences in associative learning","name":"articletitle","label":"Article Title"},{"value":"Cell Reports Methods","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.crmeth.2025.101144","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"101144"}}