Biz onun fotoğrafını malzeme yardımında Reiko Ando teşekkür ederiz. Bu araştırma için araştırmacı araştırma Grant-in-Aid tarafından desteklenmiştir (JSP'ler KAKENHI Grant sayı 16K 15196).

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	<li>Bryan, K. J., Lee, H., Perry, G., Smith, M. A., Casadesus, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Transgenic Mouse Models of Alzheimer's Disease: Behavioral Testing and Considerations. Methods of Behavior Analysis in Neuroscience. , (2009).</li><li>Nestler, E. J., Hyman, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+neuropsychiatric+disorders.">Animal models of neuropsychiatric disorders.</a> Nature Neuroscience. 13 (10), 1161-1169 (2010).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+Phenotyping+Strategies+for+Mutant+Mice.">Behavioral Phenotyping Strategies for Mutant Mice.</a> Neuron. 57 (6), 809-818 (2008).</li><li>Zarringhalam, K., Ka, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+open+system+for+automatic+home-cage+behavioral+analysis+and+its+application+to+male+and+female+mouse+models+of+Huntington's+disease.">An open system for automatic home-cage behavioral analysis and its application to male and female mouse models of Huntington's disease.</a> Behavioural Brain Research. 229 (1), 216-225 (2012).</li><li>Prusiner, S. B., Jackson, W. S., King, O. D., Lindquist, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+power+of+automated+high-resolution+behavior+analysis+revealed+by+its+application+to+mouse+models+of+Huntington's+and+prion+diseases.">The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington's and prion diseases.</a> Proceedings of the National Academy of Sciences of the United States of America. 95 (23), 13363-13383 (1998).</li><li>Jhuang, H., Garrote, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+home-cage+behavioural+phenotyping+of+mice.">Automated home-cage behavioural phenotyping of mice.</a> Nature Communications. 1 (6), 1-9 (2010).</li><li>Krackow, S., Vannoni, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consistent+behavioral+phenotype+differences+between+inbred+mouse+strains+in+the+IntelliCage.">Consistent behavioral phenotype differences between inbred mouse strains in the IntelliCage.</a> Genes, brain, and behavior. 9 (7), 722-731 (2010).</li><li>Nilsson, P., Saito, T., Saido, T. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+mouse+model+of+Alzheimer's.">New mouse model of Alzheimer's.</a> ACS chemical. 5 (7), 499-502 (2014).</li><li>Saito, T., Matsuba, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single+App+knock-in+mouse+models+of+Alzheimer's+disease.">Single App knock-in mouse models of Alzheimer's disease.</a> Nat Neurosci. 17 (5), 661-663 (2014).</li><li>Masuda, A., Kobayashi, Y., Kogo, N., Saito, T., Saido, T. C., Itohara, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+deficits+in+single+App+knock-in+mouse+models.">Cognitive deficits in single App knock-in mouse models.</a> Neurobiology of Learning and Memory. , (2016).</li><li>Chan, R. C. K., Shum, D., Toulopoulou, T., Chen, E. Y. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+executive+functions:+Review+of+instruments+and+identification+of+critical+issues.">Assessment of executive functions: Review of instruments and identification of critical issues.</a> Archives of Clinical Neuropsychology. 23 (2), 201-216 (2008).</li><li>Jurado, M. B., Rosselli, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Elusive+Nature+of+Executive+Functions:+A+Review+of+our+Current+Understanding.">The Elusive Nature of Executive Functions: A Review of our Current Understanding.</a> Neuropsychology Review. 17 (3), 213-233 (2007).</li><li>Diamond, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Executive+Functions.">Executive Functions.</a> Annual Review of Psychology. 64 (1), 135-168 (2013).</li><li>Kobayashi, Y., Sano, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+dissection+of+medial+habenula-interpeduncular+nucleus+pathway+function+in+mice.">Genetic dissection of medial habenula-interpeduncular nucleus pathway function in mice.</a> Frontiers in behavioral neuroscience. 7, 17 (2013).</li><li>Robinson, O. J., Vytal, K., Cornwell, B. R., Grillon, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+anxiety+upon+cognition:+perspectives+from+human+threat+of+shock+studies.">The impact of anxiety upon cognition: perspectives from human threat of shock studies.</a> Frontiers in human neuroscience. 7, 203 (2013).</li><li>Robbins, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+5-choice+serial+reaction+time+task:+behavioural+pharmacology+and+functional+neurochemistry.">The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry.</a> Psychopharmacology. (3-4), 362-380 (2002).</li><li>Asinof, S. K., Paine, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+5-Choice+Serial+Reaction+Time+Task:+A+Task+of+Attention+and+Impulse+Control+for+Rodents.">The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents.</a> Journal of Visualized Experiments. (90), e51574 (2014).</li><li>Codita, A., Gumucio, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+behavior+of+female+tg-ArcSwe+APP+mice+in+the+IntelliCage:+A+longitudinal+study.">Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study.</a> Behavioural brain research. 215 (1), 83-94 (2010).</li><li>Blumstein, D. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Habituation+and+sensitization:+new+thoughts+about+old+ideas.">Habituation and sensitization: new thoughts about old ideas.</a> Animal Behaviour. 120, 255-262 (2016).</li><li>Endo, T., Maekawa, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+test+of+behavioral+flexibility+in+mice+using+a+behavioral+sequencing+task+in+IntelliCage.">Automated test of behavioral flexibility in mice using a behavioral sequencing task in IntelliCage.</a> Behavioural brain research. 221 (1), 172-181 (2011).</li><li>Voikar, V., Colacicco, G., Gruber, O., Vannoni, E., Lipp, H. -. P., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditioned+response+suppression+in+the+IntelliCage:+assessment+of+mouse+strain+differences+and+effects+of+hippocampal+and+striatal+lesions+on+acquisition+and+retention+of+memory.">Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory.</a> Behavioural brain research. 213 (2), 304-312 (2010).</li><li>Pu&#347;cian, A., &#321;&#281;ski, S., G&#243;rkiewicz, T., Meyza, K., Lipp, H. -. P., Knapska, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+automated+behavioral+test+battery+assessing+cognitive+rigidity+in+two+genetic+mouse+models+of+autism.">A novel automated behavioral test battery assessing cognitive rigidity in two genetic mouse models of autism.</a> Frontiers in Behavioral Neuroscience. 8, 140 (2014).</li><li>Voikar, V., Colacicco, G., Gruber, O., Vannoni, E., Lipp, H. -. P., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditioned+response+suppression+in+the+IntelliCage:+assessment+of+mouse+strain+differences+and+effects+of+hippocampal+and+striatal+lesions+on+acquisition+and+retention+of+memory.">Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory.</a> Behavioural brain research. 213 (2), 304-312 (2010).</li><li>Harda, Z., Dzik, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autophosphorylation+of+&#945;CaMKII+affects+social+interactions+in+mice.">Autophosphorylation of &#945;CaMKII affects social interactions in mice.</a> Genes, Brain and Behavior. , e12457 (2018).</li><li>Aarts, E., Maroteaux, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+light+spot+test:+Measuring+anxiety+in+mice+in+an+automated+home-cage+environment.">The light spot test: Measuring anxiety in mice in an automated home-cage environment.</a> Behavioural Brain Research. 294, 123-130 (2015).</li><li>Safi, K., Neuh&#228;usser-Wespy, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+anxiety+models+and+an+example+of+an+experimental+setup+using+unconditioned+avoidance+in+an+automated+system+-IntelliCage.">Mouse anxiety models and an example of an experimental setup using unconditioned avoidance in an automated system -IntelliCage.</a> Cognition Brain &amp; Behavior. 10 (4), 475-488 (2006).</li><li>Dzik, J. M., Pu&#347;cian, A., Mijakowska, Z., Radwanska, K., &#321;&#281;ski, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PyMICE:+APython+library+for+analysis+of+IntelliCage+data.">PyMICE: APython library for analysis of IntelliCage data.</a> Behavior Research Methods. 50 (2), 804-815 (2018).</li></ol>

Hiçbir çıkar çatışmaları ilan etti.

Bu kağıt genetiği değiştirilmiş reklam modelleri uzun vadeli bilişsel ve davranışsal deneyleri için otomatik ev-kafes izleme sistemi kullanma yöntemini açıklar. Transponder uygun pozisyonda implantasyonu en önemli adımdır. İmplantasyon gerçekleştirmeden önce Bu transponder son kullanma tarihi geçti değil emin olun. İkinci önemli nokta özellikle küçük bir sorun daha sonra daha ciddi bir çalışma sırasında olabilir gibi günlük, sisteminin işleyişi kontrol etmektir (i.e., bir yı...

Hayvan modellerinde nöron hastalığı geliştirme son on yılda bunların temelinde ve tedavi edici gelişmeler1,2,3teşvik için mekanik anlamak sağlamıştır. Genetik hayvan modellerinde yüksek üretilen iş davranış testi pil uygulamadır insan hastalıklarının temel mekanizmaları ve kimlik ilaç araştırmak için bir sezgisel araştırma aracı. Araştırma testi piller yaşlanma uzun vadeli gözlem için uyarlanmış ve/veya demans modelleri geleneksel olarak laboratuvarlar özel insan gücü ve zaman büyük miktarlarda tüketmek zorunda. İnsanlar tarafından davranış gözlem maliyetini azaltmak gibi bir ev-kafes izleme sistemi maliyet-etkin bir strateji olacaktır. Bazı araştırma ekipleri tek bir bireyin davranış fenotipleme bir küçük ev kafes4,5,6' yardımcı otomatik görme gücü-esaslı araçları geliştirdik. Ancak, bu tür yöntemleri sosyal etkileşim, test ortamları boyutunu ve çeşitli bilişsel fonksiyonları arasında davranış önlemleri sınırı. IntelliCage sosyal ev kafese çeşitli bilişsel görevlerini gerçekleştirmek için tasarlanmış bir ikinci nesil ev-kafes izleme sistemidir. Önemlisi, bu yöntem her gün o sağlar bize uzun vadeli davranış bilişsel işlevler değerlendirilmesi ile izleme gerçekleştirmek için işleme ortadan kaldırabilir ve özel pratik kullanım gereksinimini ortadan kaldırmak ve son derece tekrarlanabilir etkinleştirmek veri alma7. Burada, biz uzun vadeli tarif fenotipleme ve doğrulama Alzheimer hastalığının olmuştur (AD) genetik fare modellerinde oluşturulan son zamanlarda ev-kafes otomatik izleme kullanarak8,9,10 sistem. Değerlendirmeler kayma öğrenme ve yönetim işlevleri dahil, bir test pil art arda birden çok yaş noktalarda (9 – 12 ve 14 – 17 aylık) gerçekleştirildi. Bu yaş bağımlı fenotipleme genler geçici ve/veya kalıcı etkileri çeşitli bilişsel yanları hakkında tanımlamak izin verdi. Bulduğumuz bazı reklam modelleri geçici ve kalıcı fenotipleri otomatik ev-kafes izleme sistemi10kullanarak uzun vadeli analizde test çeşitli bilişsel yönlerini gösterdi. Böylece, ev-kafes izleme sistemi kullanarak otomatik çalışma yararlı ve uzun vadeli davranış fenotipleme ve doğrulama bilişsel işlev bozukluğu çeşitli modelleri için düşük maliyetlidir.

<table><tbody><tr><td>IntelliCage</td><td>TSE Systems</td><td>-</td><td>Parchased in 2011 or later</td></tr><tr><td>PC</td><td>Dell</td><td>Inspiron 580s</td><td>-</td></tr><tr><td>Display</td><td>Dell</td><td>SI75T-WL</td><td>-</td></tr><tr><td>ALPHA-dri</td><td>Shepherd Specialty Papers</td><td>-</td><td>Standard bedding</td></tr><tr><td>Aron Alpha (Krasy Glue) 2 g</td><td>Toagosei (Krasy Glue)</td><td>#04612</td><td>Cyanoacrylates for gluing magnet and blak arm</td></tr><tr><td>Handheld Transponder Reader</td><td>BTS-ID</td><td>R-560</td><td>Transponder reader, which reads both Trovan and DataMars</td></tr><tr><td>Transponder</td><td>DataMars</td><td>T-VA, T-VAS, or another series</td><td>Basic package of transponders and implanters</td></tr><tr><td>Diamond Grip Plus</td><td>Ansel Microflex</td><td>DGP-INT-M</td><td>Experimental glove</td></tr><tr><td>Isoflurane</td><td>Pfizer</td><td>1119701G1092</td><td>-</td></tr><tr><td>Vaporizer for small animals</td><td>DS Pharma Biomedical</td><td>SF-B01</td><td>Facemask included</td></tr><tr><td>Neo-Medrol</td><td>Pfizer</td><td>006472-001</td><td>Eye ointment</td></tr><tr><td>Ethanol (70%)</td><td>-</td><td>-</td><td>-</td></tr><tr><td>Excel</td><td>Microsoft</td><td>00202-51382-15524-AA928</td><td>For data analysis</td></tr></tbody></table>

automated, long-term behavioral assay for cognitive functions in multiple genetic models of alzheimer's disease, using intellicage

Multipl faktörler — yaşlanma ve genler gibi — sık bilişsel gerileme ile ilişkilidir. Alzheimer hastalığı (Ah), gibi bilişsel gerileme genetiği değiştirilmiş fare modelleri temel mekanizmaları aydınlatmak ve tedavi edici gelişmeler teşvik için umut verici bir araç haline gelmiştir. Doğrulama ve modelleri, reklam, bilişsel gerileme söz konusu olduğunda beklenen davranış anormallik karakterizasyonu bir önemli adımdır. Uzun vadeli davranışsal araştırma araştırmacılar gelen talep önemli çabalar yaşlanma etkisini incelemek için laboratuvar hayvanların. Günlük insan işleme gereksinimini ortadan kaldıran bir yüksek işlem hacmi ve düşük maliyetli test pil fareler için IntelliCage sistemidir. Burada, biz nasıl sistem içinde bir genetik Alzheimer hastalığı modelinin fenotipleme uzun süreli kullanıldığında tarif özellikle bilişsel işlevler üzerinde duruluyor. Deneme kayma öğrenme ve yönetim işlevleri değerlendirmek testlerin tekrarlanan pil kullanır. Bu düşük maliyetli yaş bağımlı fenotipleme genler geçici ve/veya kalıcı etkileri çeşitli bilişsel yanları hakkında tanımlamak için bize izin verir.

Bizim önceki çalışmada, Yaş bağımlı bilişsel açıkları reklam modelleri kullanarak otomatik ev-kafes izleme sistemi10deneyler tarafından tespit edildi. Performanslarını reklam modelleri PP genç yetişkinler ve büyük konularda olduğu gibi; Ancak, PPR performansında önemli ölçüde ve giderek oldu Engelliler (Şekil 6). Genel davranış ya da anksiyete gibi özellikleri biliş15etkileyebilir ?...

Watch this Scientific Journal Video about Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage at JoVE.com

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

Bu kağıt edimsel Klima otomatik yüksek üretilen iş davranış izleme sistemi IntelliCage sistemini kullanarak Alzheimer hastalığı genetik modelleri için bilişsel değerlendirme için bir protokol açıklar.

Otomatik, Alzheimer hastalığının IntelliCage kullanarak, birden çok genetik modellerinde bilişsel işlevler için uzun vadeli davranış tahlil

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive ...

automated-long-term-behavioral-assay-for-cognitive-functions-multiple

Research

JoVE Journal

Behavior

12.1K Görüntüleme.  RIKEN. Bu kağıt edimsel Klima otomatik yüksek üretilen iş davranış izleme sistemi IntelliCage sistemini kullanarak Alzheimer hastalığı genetik modelleri için bilişsel değerlendirme için bir protokol açıklar.

Video: Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the &#34;cloud&#34; and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in&#160;cabinet; two such cabinets (16 environments) may be controlled by one computer.

Fully automated system for measuring physiologically meaningful properties of the mechanisms mediating spatial localization, temporal localization, duration, rate&#160;and probability estimation, risk assessment, impulsivity, and the accuracy and precision of memory, in order to assess the effects of genetic and pharmacological manipulations on foundational mechanisms of cognition in mice.

Farelerin Otomatik, Kantitatif / Bilişsel Davranışçı Tarama: Genetik, Farmakoloji, Hayvan Biliş ve Lisans Öğretim İçin

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and ...

Davranış

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

Entegre Davranış İstasyonu ile Kemirgen Hastalık Modellerinin Davranış Fenotiplendirme (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their behavioral flexibility and required memory duration, the number of goals and pathways, and also the overall task complexity. A confounding feature in many of these tasks is the lack of control over the strategy employed by the rodents to reach the goal, e.g., allocentric (declarative-like) or egocentric (procedural) based strategies. The double-H maze is a novel water-escape memory task that addresses this issue, by allowing the experimenter to direct the type of strategy learned during the training period. The double-H maze is a transparent device, which consists of a central alleyway with three arms protruding on both sides, along with an escape platform submerged at the extremity of one of these arms.
Rats can be trained using an allocentric strategy by alternating the start position in the maze in an unpredictable manner (see protocol 1; &#167;4.7), thus requiring them to learn the location of the platform based on the available allothetic cues. Alternatively, an egocentric learning strategy (protocol 2; &#167;4.8) can be employed by releasing the rats from the same position during each trial, until they learn the procedural pattern required to reach the goal. This task has been proven to allow for the formation of stable memory traces.
Memory can be probed following the training period in a misleading probe trial, in which the starting position for the rats alternates. Following an egocentric learning paradigm, rats typically resort to an allocentric-based strategy, but only when their initial view on the extra-maze cues differs markedly from their original position. This task is ideally suited to explore the effects of drugs/perturbations on allocentric/egocentric memory performance, as well as the interactions between these two memory systems.

The goal of this protocol is to investigate spatial cognition in rodents. The double-H water maze is a novel test, which is particularly useful to elucidate the different components of learning, consolidation and memory, as well as the interplay of memory systems.

Çift H Maze: Kemirgenler A Sağlam Davranış Öğrenme için test ve Hafıza

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their ...

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer&#8217;s disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer&#8217;s disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences.

Morris Water Maze Testi: Fare Gerilme ve Test Ortamı için Optimizasyon

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of &alpha;-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that &alpha;-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that &alpha;-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

This article presents the protocol of T-maze tests using a modified automated apparatus for assessing the learning and memory functions in mice.

T-labirent Zorla Değişim ve Çalışma ve Fareler Referans Bellek değerlendirilmesi için sağ-sol Ayrımcılık Görevler

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in ...

Nörobilim

A Fully Automated and Highly Versatile System for Testing Multi-cognitive Functions and Recording Neuronal Activities in Rodents

We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be investigated in a single task sequence. The unique feature of this system is a custom-made, acoustically transparent chamber that eliminates many of the issues associated with auditory cue control in most commercially available chambers. The ease with which operant devices can be added or replaced makes this system quite versatile, allowing for the implementation of a variety of auditory, visual, and olfactory behavioral tasks. Automation of the system allows fine temporal (10 ms) control and precise time-stamping of each event in a predesigned behavioral sequence. When combined with a multi-channel electrophysiology recording system, multiple cognitive brain functions, such as motivation, attention, decision-making, patience, and rewards, can be examined sequentially or independently.

In this report, we present a fully automated and highly versatile system capable of simultaneously testing multi-cognitive behaviors and recording neuronal activities for rodents.

Multi-bilişsel işlevler Test ve Kemirgenler Nöronal Etkinlikler kayıt için Tam Otomatik ve Çok Yönlü Sistemi

We have developed a fully automated system for operant behavior testing and neuronal activity recording by which multiple cognitive brain functions can be ...

Intracerebroventricular Injection of Amyloid-&#946; Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits

Amyloid-&#946; (A&#946;) is a major pathological mediator of both familial and sporadic Alzheimer's disease (AD). In the brains of AD patients, progressive accumulation of A&#946; oligomers and plaques is observed. Such A&#946; abnormalities are believed to block long-term potentiation, impair synaptic function, and induce cognitive deficits. Clinical and experimental evidences have revealed that the acute increase of A&#946; levels in the brain allows development of Alzheimer-like phenotypes. Hence, a detailed protocol describing how to acutely generate an AD mouse model via the intracerebroventricular (ICV) injection of A&#946; is necessary in many cases. In this protocol, the steps of the experiment with an A&#946;-injected mouse are included, from the preparation of peptides to the testing of behavioral abnormalities. The process of preparing the tools and animal subjects before the injection, of injecting the A&#946; into the mouse brain via ICV injection, and of assessing the degree of cognitive impairment are easily explained throughout the protocol, with an emphasis on tips for effective ICV injection of A&#946;. By mimicking certain aspects of AD with a designated injection of A&#946;, researchers can bypass the aging process and focus on the downstream pathology of A&#946; abnormalities.

The amyloid-&#946; (A&#946;)-injected animal model enables the administration of a defined quantity and species of A&#946; fragments and reduces individual differences within each study group. This protocol describes the intracerebroventricular (ICV) injection of A&#946; without stereotactic instruments, enabling the production of Alzheimer-like behavioral abnormalities in normal mice.

Normal Farelerde Amiloid-β Peptitler intraserebroventriküler enjeksiyon Akut Alzheimer gibi Bilişsel Açıkları tetikleyebilecek

Amyloid-&#946; (A&#946;) is a major pathological mediator of both familial and sporadic Alzheimer's disease (AD). In the brains of AD patients, ...

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke.
For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

To investigate the co-morbid Alzheimer&#39;s disease (AD) and stroke condition in a novel model, three behavior tasks are described that assess both motor control and cognitive behaviors. These tasks include the beam-walk task, cylinder task and Morris water maze.

İnme ile Alzheimer Hastalığının bir Transgenik Fare Modelinde Motor ve Hipokampal Bağımlı Mekansal Öğrenme ve Referans Hafıza Değerlendirme

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

Tıp

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-&#946; and Tau Neuropathology

Here we describe a staged, behavioral testing approach that can be used to screen for compounds that exhibit in vivo efficacy on cognitive and functional motor behaviors in transgenic mouse models of &#946;-amyloidosis and tauopathy. The paradigm includes tests for spontaneous alternation in a Y-maze, novel object recognition, and limb clasping. These tests were selected because they: 1) interrogate function of cognitive or motor domains and the correlate neural circuitry relevant to the human disease state, 2) have clearly defined endpoints, 3) have easily implementable quality control checks, 4) can be run in a moderate throughput format, and 5) require little intervention by the investigator. These methods are designed for investigators looking to screen compounds for activity in short-term and working memory tasks, or functional motor behaviors associated with Alzheimer's disease mouse models. The methods described here use behavioral tests that engage a number of different brain regions including hippocampus and various cortical areas. Investigators that desire cognitive tests that specifically assess cognition mediated by a single brain region could use these techniques to supplement other behavioral tests.

Described here is a staged, behavioral screening approach that can be used to screen for compounds that exhibit in vivo efficacy on cognitive and functional motor behaviors in transgenic mouse models of &#946;-amyloidosis and tauopathy. These methods are optimized to screen compounds for activity in short-term and working memory tasks.

Amiloid-β ve Tau Nöropatolojisinin Transgenik Fare Modellerinde Spontan Dalgalanmanın Değerlendirilmesi, Yeni Nesne Tanıma ve Limb Klapması

Here we describe a staged, behavioral testing approach that can be used to screen for compounds that exhibit in vivo efficacy on cognitive and functional ...

Shuttle Box Assay as an Associative Learning Tool for Cognitive Assessment in Learning and Memory Studies using Adult Zebrafish

Cognitive deficits, including impaired learning and memory, are a primary symptom of various developmental and age-related neurodegenerative diseases and traumatic brain injury (TBI). Zebrafish are an important neuroscience model due to their transparency during development and robust regenerative capabilities following neurotrauma. While various cognitive tests exist in zebrafish, most of the cognitive assessments that are rapid examine non-associative learning. At the same time, associative-learning assays often require multiple days or weeks. Here, we describe a rapid associative-learning test that utilizes an adverse stimulus (electric shock) and requires minimal preparation time. The shuttle box assay, presented here, is simple, ideal for novice investigators, and requires minimal equipment. We demonstrate that, following TBI, this shuttle box test reproducibly assesses cognitive deficit and recovery from young to old zebrafish. Additionally, the assay is adaptable to examine either immediate or delayed memory. We demonstrate that both a single TBI and repeated TBI events negatively affect learning and immediate memory but not delayed memory. We, therefore, conclude that the shuttle box assay reproducibly tracks the progression and recovery of cognitive impairment.

Learning and memory are potent metrics in studying either developmental, disease-dependent, or environmentally induced cognitive impairments. Most cognitive assessments require specialized equipment and extensive time commitments. However, the shuttle box assay is an associative learning tool that utilizes a conventional gel box for rapid and reliable assessment of adult zebrafish cognition.

Yetişkin Zebra Balığı Kullanarak Öğrenme ve Bellek Çalışmalarında Bilişsel Değerlendirme için İlişkisel Bir Öğrenme Aracı Olarak Mekik Kutusu Tahlil

Cognitive deficits, including impaired learning and memory, are a primary symptom of various developmental and age-related neurodegenerative diseases and ...