Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates Kimiko Shimizu, Ken-ichi Inoue, Takao Oishi, Masahiko Takada, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2013762/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cognitive functions depend on the time of day in various organisms. Previously, we found that 24-hour recognition memory performance of nocturnal mice changes diurnally through SCOP protein-dependent regulation. It remains unknown whether SCOP-dependent regulation of memory performance is conserved across species with diurnal/nocturnal habits. We tested whether the time of day affects the memory performance of diurnal Japanese macaques. The memory association between bitter taste of drinking water and the nozzle color of the water bottle was established during the light period of the day to evaluate of memory performance for macaques. Here we found diurnal variation of declarative memory in Japanese macaques. The middle of the daytime is the most effective time for memory performance during the light period. To assess whether SCOP is involved in declarative memory performance, we interfered with SCOP expression by using lentiviral vector expressing shRNA against Scop. Scop knockdown in the hippocampus abrogated the memory performance in the middle of the daytime. Our results implicate that SCOP in the hippocampus is necessary for the diurnal rhythm of the memory system and that the SCOP-dependent memory regulation system could be conserved in mammals. Biological sciences/Neuroscience/Circadian rhythms and sleep Biological sciences/Neuroscience/Cognitive neuroscience Biological sciences/Neuroscience/Learning and memory Biological sciences/Neuroscience/Molecular neuroscience Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations No competing interests reported. Supplementary Files supplementalfigure.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2013762","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":148140311,"identity":"239c557a-dee3-4782-bcc3-054f86172704","order_by":0,"name":"Kimiko Shimizu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDACCcYGxgYgbcAOJHnAQgeI1cJzmGgtDAwQLRLJMC0EgPzs5taNMxjuyJtLvj+64Q2DnTwD41n81hjcOdh2cwPDM8Ods5PZbs5hSDZsYDiXgF+LRGLbzQcMhxMMbiez3eZhYAYqP2OA32EzYFpuHgZpqSesheFGIshhQC03mEFaDhPWYgDSMsMA6JeeZLObcwyOG7YR8ov8jPRnN3sqgCHGfvDZjTcV1fL8EgRCDGoXTBHQSWwSZ4jQgRrh/D1EaRkFo2AUjIKRAwDJBU2mFEoWkAAAAABJRU5ErkJggg==","orcid":"","institution":"Tokyo Medical and Dental University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kimiko","middleName":"","lastName":"Shimizu","suffix":""},{"id":148140312,"identity":"a89bc3be-99dc-463b-919d-21e5c0ac88fd","order_by":1,"name":"Ken-ichi Inoue","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ken-ichi","middleName":"","lastName":"Inoue","suffix":""},{"id":148140313,"identity":"3da42162-6f8a-40be-a7b3-1003abef38cc","order_by":2,"name":"Takao Oishi","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Takao","middleName":"","lastName":"Oishi","suffix":""},{"id":148140314,"identity":"7a9df217-c6ee-4f4d-bff9-8ce9cb99b845","order_by":3,"name":"Masahiko Takada","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masahiko","middleName":"","lastName":"Takada","suffix":""},{"id":148140315,"identity":"9c28e735-3b14-4834-bffa-2130a751afb4","order_by":4,"name":"Yoshitaka Fukada","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yoshitaka","middleName":"","lastName":"Fukada","suffix":""},{"id":148140316,"identity":"b26d4007-5298-44c4-ae3e-d969f81c73c5","order_by":5,"name":"Hiroo Imai","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiroo","middleName":"","lastName":"Imai","suffix":""}],"badges":[],"createdAt":"2022-08-30 11:59:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2013762/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2013762/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":28564589,"identity":"980bf8d9-4da9-4d72-8892-40030b7b67af","added_by":"auto","created_at":"2022-11-02 14:39:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20747,"visible":true,"origin":"","legend":"\u003cp\u003eDaily water consumption from regular water supply system\u003c/p\u003e\n\u003cp\u003eSeveral days of water consumption of two macaques in 12-hour light/dark condition. Blue\u003c/p\u003e\n\u003cp\u003edots are water drops the monkey consumed per 5 minutes. The monkeys are fed three times a\u003c/p\u003e\n\u003cp\u003eday: ZT 1.5, ZT5.5, and ZT10.0 during a daytime.\u003c/p\u003e","description":"","filename":"SARU202208301.png","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1/c280b2dc6146712a3b2a38dd.png"},{"id":28564585,"identity":"2991d83d-d4fa-460c-9fe5-ed24dd8613e0","added_by":"auto","created_at":"2022-11-02 14:39:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":231942,"visible":true,"origin":"","legend":"\u003cp\u003eDiurnal change of color-taste association task\u003c/p\u003e\n\u003cp\u003e(a) A Japanese macaque in a cage with two water bottles. (b) The method for the color-taste\u003c/p\u003e\n\u003cp\u003eassociation task. The color-taste association task is done in five consecutive days consisting\u003c/p\u003e\n\u003cp\u003eof three parts, three days of “practice”, one day of “training”, and one day of “testing” at\u003c/p\u003e\n\u003cp\u003eeither three-time points, ZT 1.5 (Group 1), ZT 5.5 (Group 2), or ZT 10 (Group 3). In the\u003c/p\u003e\n\u003cp\u003e“practice,” two bottles of bitter water and normal water equipped with nozzles in different\u003c/p\u003e\n\u003cp\u003ecolors were presented to the monkeys. The “practice” let animals learn that nozzle color is\u003c/p\u003e\n\u003cp\u003eassociated with water taste. Monkeys were allowed to freely drink water from the bottles for 2\u003c/p\u003e\n\u003cp\u003ehours with the location exchange at 1-hour after the bottle setting. “Training” and “testing”\u003c/p\u003e\n\u003cp\u003ewere carried out at the same time of day as the “practice,” and nozzle color sets are the same\u003c/p\u003e\n\u003cp\u003ein the “training” and “testing” but different from those used in the “practice.” In the\u003c/p\u003e\n\u003cp\u003e“training,” the bottles are presented for 2 hours with the location exchange at 1-hour after the\u003c/p\u003e\n\u003cp\u003ebottle setting. In the “testing,” the two bottles were both filled with normal water, and the\u003c/p\u003e\n\u003cp\u003eanimals were allowed to drink water from the bottles for 30 minutes, with the location\u003c/p\u003e\n\u003cp\u003eexchanged at 15-minute after the bottle setting. An association between specific nozzle color\u003c/p\u003e\n\u003cp\u003eand water taste formed during the \"training” was evaluated in the” testing.” (c) The accuracy\u003c/p\u003e\n\u003cp\u003erate was examined at ZT1.5, ZT5.5, or ZT10. *p=0.002 (ZT5.5) by Student’s t-test (versus\u003c/p\u003e\n\u003cp\u003e0.25 chance level). Error bars, s.e.m. (n=6 macaques, a total of 16 task trials for ZT1.5, 13\u003c/p\u003e\n\u003cp\u003etask trials for ZT5.5, 16 task trials for ZT10.0). The dotted line represents performance by\u003c/p\u003e\n\u003cp\u003echance 0.25. n.s., not statistically significant.\u003c/p\u003e","description":"","filename":"SARU202208302.png","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1/f57802bddb27403ba38a99e8.png"},{"id":28564586,"identity":"193e055d-0ce0-4e60-830c-7eb83646a6e9","added_by":"auto","created_at":"2022-11-02 14:39:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47929,"visible":true,"origin":"","legend":"\u003cp\u003eEvaluation for the knockdown efficiency of Scop shRNA expressing lentiviral\u003c/p\u003e\n\u003cp\u003evector\u003c/p\u003e\n\u003cp\u003e(a) Schematic diagram of the shRNA-expressing lentiviral vector. The shRNA\u003c/p\u003e\n\u003cp\u003eis controlled by the macaque H1 promoter (mkH1), and the CMV promoter drives the EGFP\u003c/p\u003e\n\u003cp\u003emarker gene for tracking transduced cells. 5’-LTR, HIV-1 5’-LTR; 3’ LTR, HIV-1 selfinactivating\u003c/p\u003e\n\u003cp\u003e3’-LTR. (b) Western blot analysis of SCOP protein level after shRNA expressing\u003c/p\u003e\n\u003cp\u003elentivirus infection. Decrease in SCOP protein level in COS7 cells by infection of anti-Scop\u003c/p\u003e\n\u003cp\u003eshRNA lentivirus (shScop). Scramble shRNA lentivirus was used as a control. The sample in\u003c/p\u003e\n\u003cp\u003eeach lane is from a different culture dish. The displayed blot was cropped from the full-length\u003c/p\u003e\n\u003cp\u003eblot in the supplemental figure.\u003c/p\u003e","description":"","filename":"SARU202208303.png","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1/abbb2b650509a8ff56033728.png"},{"id":28564587,"identity":"386cc8e2-0503-4525-ba88-9438b9dd4596","added_by":"auto","created_at":"2022-11-02 14:39:54","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":419478,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of Scop knockdown in the hippocampus on color-taste association task\u003c/p\u003e\n\u003cp\u003e(a) A representative EGFP fluorescence (green) and Hoechst 33258 (Blue) image of a\u003c/p\u003e\n\u003cp\u003ehippocampal section of the macaque that received shRNA lentivirus. The white square in the\u003c/p\u003e\n\u003cp\u003eleft photo is enlarged in the right photo. Scale bars are indicated in the photos. The white\u003c/p\u003e\n\u003cp\u003edotted area shows the hippocampal CA1 to CA4. DG, dentate gyrus; LGN, lateral geniculate\u003c/p\u003e\n\u003cp\u003enucleus. (b) Evaluation of the knockdown activity of anti-Scop shRNA lentivirus on Scop\u003c/p\u003e\n\u003cp\u003emRNA level. Decrease in Scop mRNA level in the hippocampus by infection of anti-Scop\u003c/p\u003e\n\u003cp\u003eshRNA lentivirus (Scop shRNA). Scramble shRNA lentivirus was used as a control. Error\u003c/p\u003e\n\u003cp\u003ebars, SEM (n = 6 subregions). (c) The accuracy rate for Scop knockdown and control\u003c/p\u003e\n\u003cp\u003emacaques (one each) is shown. Memory performance at ZT 5.5 (midday) in each monkey that\u003c/p\u003e\n\u003cp\u003ereceived lentivirus expressing Scop shRNA or Scramble shRNA were measured. The task was\u003c/p\u003e\n\u003cp\u003ecarried out six times for each animal. The number above each bar on the graph indicates the\u003c/p\u003e\n\u003cp\u003enumber of corrects for the number of trials.\u003c/p\u003e","description":"","filename":"SARU202208304.png","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1/675a22609c191e5edbfa794e.png"},{"id":31985567,"identity":"9dcca35b-6d0b-4b0a-9c41-8be100b5bfde","added_by":"auto","created_at":"2023-01-24 09:14:25","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":531877,"visible":true,"origin":"","legend":"","description":"","filename":"220901Scop.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1_covered.pdf"},{"id":28565671,"identity":"332df9ee-b8f4-4678-9a8d-bd8f179bbf9e","added_by":"auto","created_at":"2022-11-02 14:45:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":526212,"visible":true,"origin":"","legend":"","description":"","filename":"220901Scop.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1_covered.pdf"},{"id":28565564,"identity":"cf2c048d-d36a-4c92-96ee-d38355bb7e5a","added_by":"auto","created_at":"2022-11-02 14:44:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":192259,"visible":true,"origin":"","legend":"","description":"","filename":"supplementalfigure.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2013762/v1/1d26fa9400877d46946892db.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-2013762/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2013762/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Cognitive functions depend on the time of day in various organisms. Previously, we found that 24-hour recognition memory performance of nocturnal mice changes diurnally through SCOP protein-dependent regulation. It remains unknown whether SCOP-dependent regulation of memory performance is conserved across species with diurnal/nocturnal habits. We tested whether the time of day affects the memory performance of diurnal Japanese macaques. The memory association between bitter taste of drinking water and the nozzle color of the water bottle was established during the light period of the day to evaluate of memory performance for macaques. Here we found diurnal variation of declarative memory in Japanese macaques. The middle of the daytime is the most effective time for memory performance during the light period. To assess whether SCOP is involved in declarative memory performance, we interfered with SCOP expression by using lentiviral vector expressing shRNA against Scop. Scop knockdown in the hippocampus abrogated the memory performance in the middle of the daytime. Our results implicate that SCOP in the hippocampus is necessary for the diurnal rhythm of the memory system and that the SCOP-dependent memory regulation system could be conserved in mammals.","manuscriptTitle":"Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-02 14:39:51","doi":"10.21203/rs.3.rs-2013762/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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