Name: the use of the puzzle box as a means of assessing the efficacy of environmental enrichment
Uploaded: 2014-12-29T14:00:00.000+00:00
Duration: 6 min 50 s
Description: Watch this Scientific Journal Video about The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment at JoVE.com

The authors have no acknowledgements.

Etik deyimi: Tüm işlemler Sydney Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmış ve Ulusal Sağlık ve Avustralya kurallar Tıbbi Araştırma Konseyi uyduğu bulundu. Prosedürler University of Sydney, Bosch Kemirgen Tesisi&#39;nde yetiştirilen edildi C57 / BL6J fareler üzerinde yapıldı. Tüm fareler kuru gıda ve su ad libitum erişim ayrı ayrı havalandırılan kafeslerde 0600 saatte ışıkları ile 12 saat aydınlık-karanlık döngüsü 21 ° C ortam sıcaklığında tek yeterince havalandırılmış bir odada muhafaza edildi. Geç gebelik kadın rastgele standart veya çevre zenginleştirilmiş konut koşulları ayrıldı. 1. Konut (Zenginleştirme Düzeyleri): <ol><li> 4 geç gebelik yetişkin dişi fareler elde. Rasgele standart duruma 2. atamak ve bir kırmızı fare Eskimo içeren bir temiz standart fare kafes (genel boyutları 391 x 199 x 160 mm) içine bunların her yer. Zenginleştirilmiş durum için, Rema yerleştirinining tek temiz sıçan büyüklüğünde kafesin içine 2 fareler (genel boyutları x 404 mm x 462 403). </li><li> Zenginleştirme kafesin içine, bir duyusal ve motor uyarımı artırmak için tasarlanan nesnelerin çeşitli (örneğin çalışan tekerlekleri, görsel uyaranlara, kokulu pamuk topları, Velcro şeritler) yerleştirin. </li><li> Her 2 ila 3 gün kafesin içinde yaklaşık bu nesneleri hareket; tahrip edilmiş herhangi bir yenileyin. </li><li> Onlar yetiştirildik çevre koşulu ile uyumlu erkek-dişi ayrılmış yuvaya 21 gün postnatal, seks hayvanlar ve yerde sütten sonra. Zenginleştirilmiş durum için 2 ile kafes başına 3 ve 10 fare ve standart 5 fareler arasında bulunmadığından emin olun. Hayvanlar yetişkinlik (12-14 hafta) ulaştıktan sonra davranışsal test başlar. </li></ol> Bulmaca Box 2. İnşaatı <ol><li> 6 Beyaz akrilik parçaları (veya diğer non-gözenekli malzeme) edinin: bir 750 x 280 mm, iki 280 x 250 mm, iki 750 x 250 mm ve 150 x 280 bir mm (Şekil 1). </li><li> 40 x 40 mm kare açılması bu parçanın bir tarafında oyulmuş ile, siyah akrilik tek parça 280 x 250 mm edinin (Şekil 1). </li><li> Aşağıdaki gibi Puzzle Kutusu birleştirin: kutusunun alt olarak 750 x 280 mm parça kullanın, kutunun uçları ve kutunun kenarlarına olarak 750 x 250 mm adet olarak 280 x 250 mm parçalarını kullanın. </li><li> Kutunun alt ile açılış floş (büyük bir, bir küçük) bir ucundan kutuya 150 mm ölçün, ve iki bölmeleri böler, böylece kutunun üzerinde akrilik siyah parça yerleştirin. </li><li> Beyaz akrilik 150 x 280 mm parça alır ve karanlık bir &quot;amaç-box&quot; odasını sağlayan, emin tamamen bu alanı kaplamaktadır yapma kutusunun küçük bölmesine tepesinde yerleştirin. Menteşe ile ana kutu gövdesine akrilik bu parça yapıştırmayın veya tamamen davranışsal test sırasında kaldırılacak ücretsiz bırakın. </li><li> Akrilik (üç 4 x 120 mm) 3 adet alın ve bir &quot;U-Shap yapmak katılmaked &quot;kanalı. </li></ol><img alt="Şekil 1," fo:content-width="5in" src="/files/ftp_upload/52225/52225fig1highres.jpg" width="500" /> Şekil 1: Bulmaca Kutusu görevin şematik. Bulmaca Kutusu açık alan bölgede (600 x 280 mm) ve tüm 750 x 280 mm ölçülerinde bir korunaklı gol kutu alanı (150 x 280 mm), oluşan bir akrilik kutu. Bu iki bölgeyi ayıran bölme (gri) içinde bir 40 x 40 mm açılış hayvanlar açık alanda karşılanır gol kutusu alanına erişmenizi sağlar. Bu açılış testi ilerledikçe kaldırmak için giderek daha zor olan engeller ile bloke edilir. Hayvanlar Her durum için üç denemeler dört tıkanıklığı koşulları oluşan, beş günlük protokolü tabi. Bulmaca Kutusu Görev 3. Koşu <ol><li> İyice% 70 alkol ile Bulmaca Kutusu temizleyin. Test edilen her hayvan arasındaki bu adımı tekrarlayın. </li><li> Amaç-box ar içinde temiz bir kırmızı fare Eskimo yerleştirinBulmaca Box adet ve amaç-box kapağı değiştirin. </li><li> Test edilen bir engel durum varsa, hedefe kutunun kapı içinde tıkanıklığı yerleştirin (Şekil 2). </li><li> Fare amacı-box yönelik Bulmaca Box açık alan bölümünde, içine test ve amaç-box uzak ucundan olmak yerleştirin. </li><li> Bulmaca Box amacı kutusu bölümüne girmek için hayvanın dört pençeleri için geçen süreyi kaydedin. </li><li> Bir hayvan hedef kutusu girmezse ayarlanan süre sınırı (Tablo 1) ulaşıldığında, deneme sonlandırmak. </li><li> Bir deneme bittikten sonra, Bulmaca Kutusu hayvan kaldırmak ve bir sonraki duruşma başlayana kadar ayrı tutma kafes içine yerleştirin. Her hayvan için denemeler arasında 60-180 sn boşluk bırakın. </li><li> Her bir hayvan için, dört tıkanıklığı koşulları ve her bir durumda üç denemeler ile test beş ardışık gün için, günde üç denemeler gerçekleştirmek. Üçüncü triBelirli bir tıkanma durumunun ark, her zaman bir sonraki gün uygulanır gerekmektedir (Tablo 1 e bakınız). </li></ol><img alt="Tablo 1" fo:content-width="5in" src="/files/ftp_upload/52225/52225table1.jpg" width="500" /> Tablo 1: Bulmaca Kutusu görev şeması. Bulmaca Kutusu görev beş gün boyunca koşmak ve dört tıkanıklığı koşulları oluşur. Üç ila dört gün her bir ilgili çalışmalar ve beşinci günde bir vardır. Her engel durumu üç denemeler vardır; bir gün ilk iki ve üçüncü gün hemen ardından. Bir engel durumun ilk deneme yerli problem çözme yeteneğini test etmeyi amaçlamaktadır, ikinci deneme görev edinimi ve takviye inceler ve üçüncü deneme çözümü tutma ve hatırlama için bir tahlil olarak kullanılır. <img alt="Şekil 2," fo:content-width="6in" src="/files/ftp_upload/52225/52225fig2highres.jpg" width="600" /> Şekil 2: Engelbulmaca Kutu görev içinde iyon koşulları. Bulmaca Kutusu arena ve bu çalışma kapsamında kullanılan tıkanıklığı koşulları şematik diyagramlar. (A) Durum 0 (C0), açık alan ve hedef kutusu alanları arasındaki kapı içinde herhangi bir engel varken. (B) Durum 1 (C1 ), açık alan ve amaç-box alanlar arasındaki kapı içinde bir &quot;u şeklindeki&quot; kanal varken. (C) kanal temiz yatak malzemesi ile doldurulmuştur Durum 2 (C2),. (D) Durum 3 (C3 ), açık alan ve hedef kutusu alanları arasındaki kapı içinde bulunan bir &quot;doku fişi&quot; ile. (E) açık alan ve hedef kutusu arasında kapı içinde bulunan bir &quot;köpük fişi&quot; ile Koşul 4 (C4) alanlar. Yöntem ve Şekil 1&#39;de göre arena boyutları. Verilerin 4. Yorumlama <ol><li> Zaman ya com alınan verileri Temsilveya null çalışmaların sayısı olarak (null hayvanlar belirlenen süre içinde görevi tamamlamak vermedi çalışmalarda dahil) deneme tamamlar. </li><li> Arası konular faktör olarak tıkanıklık tipi / durumu (C) ve görev numarası (T) içinde-konular faktörler ve (zenginleştirilmiş karşı standart) zenginleştirme seviyesi ile, bulmaca Box içinde performans üzerine konut durumun etkisini değerlendirmek için tekrarlayan ölçümler ANOVA kullanın . </li></ol>

The authors declare they have no competing financial interests.

sunulan veriler Bulmaca Kutusu etkin olarak kullanılabilir EE etkisini değerlendirmek için ortaya koymaktadır. Zenginleştirilmiş ortamlarda yetiştirilen Fareler sürekli standart laboratuar koşullarında içinde yükseltilmiş hayvanlar yaptım daha bu davranış tahlilinde içinde tıkanma bulmacaları çözmek için önemli ölçüde daha az zaman aldı. Üstelik, bu fark EE görev tarafından sunulan problemlere çözüm güçlendirmek veya korumak için kendi kapasitesine göre bir hayvanın doğal sorun ç?...

Çevre zenginleştirme (EE) sürekli hakkında getirerek, hayvanların davranışlarını etkilediği gösterilmiştir sosyal etkileşim, motor aktivite ve genellikle standart bir laboratuar environment.EE deneyimli daha fazla duyusal stimülasyon için artan fırsat hayvanları sağlayan çevresi olarak tanımlanabilir Böyle öğrenme ve bellek görevleri stres ve anksiyete ile ilgili faaliyet 8-10 azaltılması, geliştirilmiş performans gibi değişiklikler 8,11, motor koordinasyon ve keşif faaliyeti 11, bağımlılık yapan maddeler anne bakımı 8 yanı sıra direnç değişikliklerin erken başlangıçlı 12- 15. Bundan başka, EE başlangıcının geciktirilmesi ve Huntington 1-4,16, Parkinson 17 ve Alzheimer hastalığı 18 hayvan modellerinde belirtilerin şiddetinin azaltılması, nörodejeneratif bozuklukların etkisini iyileştirmek için ortaya konmuştur. Bu değişiklikler, korEE beyne boyunca uyardığı bilinmektedir anatomik ve moleküler değişikliklerle birlikte ilgilidir. Gelişiminin erken aşamalarında zenginleştirilmiş ortamlarda yetiştirilen hayvanlar 9,2-22 ve sinaptik yoğunluğu 23 dallanma dendritik artan beyin ağırlığı ve kortikal kalınlık dahil nöral değişikliklerin sayısız, göstermektedir. EE düzeyi ve hızlandırılmış duyusal 25,26,28,29 gelişimi, hafıza 30, hem de motor devrelerinde 31,32 katkı gösterilmiştir büyüme faktörü 9,24-30, zamanlama ikisini değiştirebilmektedir. Dikkate bireysel çalışmalar 9,24,27,30 içinde kullanılan hayvanların ve ortamlarda farklı almadan, EE etkisini araştıran bir önceki iş süreleri çelişkili bulgular ortaya koymuştur. Şu anda, farklı suşları ve spec çeşitli EV paradigmaların etkinliğini ölçmek için kullanılabilecek hiçbir tutarlı ve basit davranışsal bir görev olduğunuHayvanların ler. Bulmaca Kutusu görevi bir hayvanın doğal problem çözme yeteneğini 7 belirlemek için basit bir test olarak tasarlanmıştır. Açık alanda yerleştirilen hayvanlar kapalı bölge / barınak erişmek için küçük bir açılış içinde yer malzemelerin engel çıkarmak için gereklidir. Her konu üç farklı bilişsel özelliklerini değerlendirmek için aynı tıkanıklığı üç deneme verilir. İlk deneme doğasında ya da yerli problem çözme yeteneği temel gösterge verir. Aynı gün çalışacak, ikinci deneme, üzerine geliştirmek ve böylece belirli tıkanıklığı kaldırmak için stratejiler güçlendirmek için hayvanın yeteneğini bazı gösterge verir. ertesi gün yapılan üçüncü deneme, görev öğrendim çözüm korumak ve hatırlamak için konunun yeteneği içgörü sağlar. hayvanlar tarafından bu &quot;engel bulmaca&quot; çözmek için motivasyon potansiyel, değiştirilebilirAçık alanlar önlemek ve çevrelerini 6,7 keşfetmek için barınak, hem de içsel bir sürücü aramak için doğuştan gelen bir istek çağrıştıran. Bulmaca Kutusu çözmek arzusu altında yatan potansiyel davranış sürücülerin çokluğu beynin çeşitli alanlarda görev performansını aracılık yer aldığını göstermektedir. Önceki çalışma şizofreni kemirgen modellerinde, prefrontal korteks gibi hipokampus bu görevin 5 edinme yer olduğunu göstermiştir. Sıçanlarda bir lezyon çalışma, çeşitli talamik çekirdekler, hipotalamus, beyincik ve limbik yapılar içeren bulmaca Kutu performans dahil beyin bölgelerinin çok sayıda ortaya çıkarmıştır. Birlikte, bu bulgular görevi çözme bu sorunun yapan bilişsel işlev ile ilişkili sinir yapıların bir dizi içerdiğini göstermektedir. Bulmaca Kutusu m tarafından sergilenen farelerin problem çözme yeteneğini, yanı sıra bilişsel açıkları değerlendirmek için başarıyla kullanılmaktadırŞizofreni 5-7 idrar modelleri. Görev Performans derece tutarlı olması ve diğer bilişsel davranış testleri 6 sonuçları ile iyi bir korelasyon olduğu gösterilmiştir. Bu çalışmanın amacı EE etkinliğini belirleyen basit ve güvenilir bir aracı haline Puzzle Kutu görevi adapte böylece oldu.

<table><tbody><tr><td>Black Acrylic Board</td><td></td><td></td><td>280 x 250 mm with a 40 x 40 mm &quot;door&quot; cut into one side</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>280 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>280 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>750 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>750 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>150 x 280 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td></td></tr><tr><td>Underpass</td><td></td><td></td><td>3 pieces of 40 x 120 mm plexiglass or acrylic</td></tr><tr><td colspan="4">Note: If unable to access acrylic board, plexiglass or similar non-porous material will suffice.</td></tr><tr><td>Webcam</td><td>Logitech</td><td>C210</td><td>Fix to roof with electrical tape. Alternatively, use a tripod.</td></tr><tr><td>VirtualDub v1.10.4</td><td>VirtualDub</td><td>N/A&amp;nbsp;</td><td>Software for recording behaviour videos. Input from webcam.</td></tr><tr><td>TopScan v 3.0</td><td>CleverSys Inc.</td><td>N/A&amp;nbsp;</td><td>Software for automated top-view tracking and analysis of mouse behaviour. Captured videos are analysed post-hoc.</td></tr></tbody></table>

the use of the puzzle box as a means of assessing the efficacy of environmental enrichment

Environmental enrichment can dramatically influence the development and function of neural circuits. Further, enrichment has been shown to successfully delay the onset of symptoms in models of Huntington&#8217;s disease 1-4, suggesting environmental factors can evoke a neuroprotective effect against the progressive, cellular level damage observed in neurodegenerative disorders. The ways in which an animal can be environmentally enriched, however, can vary considerably. Further, there is no straightforward manner in which the effects of environmental enrichment can be assessed: most methods require either fairly complicated behavioral paradigms and/or postmortem anatomical/physiological analyses. This protocol describes the use of a simple and inexpensive behavioral assay, the Puzzle Box 5-7 as a robust means of determining the efficacy of increased social, sensory and motor stimulation on mice compared to cohorts raised in standard laboratory conditions. This simple problem solving task takes advantage of a rodent&#8217;s innate desire to avoid open enclosures by seeking shelter. Cognitive ability is assessed by adding increasingly complex impediments to the shelter&#8217;s entrance. The time a given subject takes to successfully remove the obstructions and enter the shelter serves as the primary metric for task performance. This method could provide a reliable means of rapidly assessing the efficacy of different enrichment protocols on cognitive function, thus paving the way for systematically determining the role specific environmental factors play in delaying the onset of neurodevelopmental and neurodegenerative disease.

Burada anlatılan sonuçlar farklı litre oluşan çeşitli gruplarda alınan verilerle, temsili bir örnek vardır. Tüm davranışsal testler kohort içinde hayvanların randomize test düzeni ile, 0700 ve 1100 saat arasında icra edilmiştir. (15, 7 kadın ve 8 erkek n =) (bkz zenginleştirilmiş bir ortamda büyüdü Hayvanlar (n = 14, 7 kadın ve 7 erkek) standart ortam içinde yükseltilmiş daha Bulmaca Kutusu içinde tıkanma görevleri çözmek için daha az zaman aldı Şekil 3) (Tekrarlanan ?...

Watch this Scientific Journal Video about The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment at JoVE.com

The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple &#8220;Puzzle Box&#8221; method for assessing an animal&#8217;s cognitive function, in order to reveal the effectiveness of environmental enrichment.

Çevre Etkilerinin Değerlendirilmesi Zenginleştirme Aracı Olarak Bulmaca Box Kullanımı

Environmental enrichment can dramatically influence the development and function of neural circuits.  Further, enrichment has been shown to successfully ...

the-use-puzzle-box-as-means-assessing-efficacy-environmental

Universidad San Sebastian

Research

JoVE Journal

Behavior

11.6K Görüntüleme.  University of Sydney. Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple “Puzzle Box” method for assessing an animal’s cognitive function, in order to reveal the effectiveness of environmental enrichment.

Video: The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

Modifiye Delik Kurulu - Fareler ve Sıçanlarda Davranışı, Biliş ve Sosyal Etkileşim Ölçme

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

Davranış

A Protocol for Housing Mice in an Enriched Environment

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of &#8216;toys&#8217; to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer.

Environmental enrichment for mice requires a complex and challenging setup, as well as comprehensive husbandry and handling techniques to assure robust metabolic and anti-cancer effects in the mice. This protocol provides detailed procedures to reproduce the above mentioned effects in mice.

Bir Zenginleştirilmiş Ortamında Konut Fareler için Protokol

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent ...

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.
Burrowing was first developed in Oxford13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.6



Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it8.



Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality5. 



A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

Burrowing, nesting, and hoarding are species-typical activities that mice readily perform in the laboratory. This article describes how they can be easily and cheaply assessed. These protocols are extremely sensitive to mouse strain, brain lesions and diseases. Moreover they constitute &#x201C;environmental enrichment&#x201D; for the mice, and embody the &#x201C;Refinement&#x201D; aspect of the &#x201C;3 Rs&#x201D;18.

Değerlendirilmesi Fare, Nest İnşaat ve İstifçiliğine Sığıntı

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening ...

Nörobilim

Novel Object Exploration as a Potential Assay for Higher Order Repetitive Behaviors in Mice

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals. RRBs are commonly split into lower-order and higher-order components, with lower order RRBs consisting of motor stereotypies and higher order RRBs consisting of perseverative and sequencing behaviors. Higher order RRBs are challenging to model in mice. Current assays for RRBs in mice focus primarily on the lower order components, making basic biomedical research into potential treatments or interventions for higher-order RRBs difficult. Here we describe a new assay, novel object exploration. This assay uses a basic open-field arena with four novel objects placed around the perimeter. The test mouse is allowed to freely explore the arena and the order in which the mouse investigates the novel objects is recorded. From these data, patterned sequences of exploration can be identified, as can the most preferred object for each mouse. The representative data shared here and past results using the novel object exploration assay illustrate that inbred mouse strains do demonstrate different behavior in this assay and that strains with elevated lower order RRBs also show elevated patterned behavior. As such, the novel object exploration assay appears to possess good face validity for higher order RRBs in humans and may be a valuable assay for future studies investigating novel therapeutics for ASD.

Higher order restricted, repetitive behaviors (RRBs) disrupt the lives of affected individuals. These behaviors are challenging to model in rodents, making basic biomedical research into potential treatments or interventions for RRBs difficult. Here we describe novel object exploration as a potential assay for higher order RRBs in mice.

Farelerde Yüksek mertebeden Tekrarlanan Davranışlar için bir potansiyel Testi olarak yeni nesne Keşif

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals.  RRBs are ...

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous research determined a profound impact of gentle handling protocols on the well-being of laboratory mice. By introducing clicker training to the keeping of mice, not only do we promote the amicable treatment of mice, but we also enable them to experience cognitive enrichment. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcer, the "click" sound of a clicker, which serves as a time bridge between the strengthened behavior and an upcoming reward. The effective implementation of the clicker training protocol with a cohort of 12 BALB/c inbred mice of each sex proved to be uncomplicated. The mice learned rather quickly when challenged with tasks of the clicker training protocol, and almost all trained mice overcame the challenges they were given (100% of female mice and 83% of male mice). This study has identified that clicker training for mice strongly correlates with reduced fear in the mice during human-mice interactions, as shown by reduced anxiety-related behaviors (e.g., defecation, vocalization, and urination) and fewer depression-like behaviors (e.g., floating). By developing a reliable protocol that can be easily integrated into the daily routine of the keeping of laboratory mice, the lifetime experience of welfare in the mice can be improved substantially.

The development of new refinement strategies for laboratory mice is a challenging task that contributes towards fulfilling the 3R principle. This protocol introduces clicker training as a cognitive enrichment program for laboratory mice.

Laboratuvar Fareler için Bilişsel Zenginleştirme olarak Clicker Eğitim Tanıtımı

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous ...

Analyzing Spatial Learning and Prosocial Behavior in Mice Using the Barnes Maze and Damsel-in-Distress Paradigms

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. The Barnes maze can also assess other mouse behaviors, such as general motivation to escape from the maze platform and exploratory behavior. The Barnes maze can measure whether a genetic mutation or environmental variable can impact the acquisition and retention of spatial memories, as well as provide information about the search strategy employed by the mice. Here we use the Barnes maze to detect a memory deficit in adult mice following a single developmental ethanol exposure event. The newly described Damsel-in-Distress paradigm exposes a male mouse to a female mouse trapped in a chamber in the open center field of the arena. It provides an opportunity for the mouse to socially respond to the trapped female and exhibit prosocial behavior. The Damsel-in-Distress paradigm can also be used to examine mouse behavior in a novel arena and measure locomotor activity. Both the Barnes Maze and the Damsel-in-Distress protocols require minimal financial investment and most aspects of the tests can be constructed from common lab supplies. These flexible and accessible tools can also be used to detect behavioral changes over the course of development.

This protocol measures spatial learning and memory using the Barnes maze. A novel Damsel-in-Distress paradigm is used to assess locomotor activity and prosocial behavior in mice.

Kayma öğrenme ve Barnes labirent ve sıkıntı içinde küçük hanım paradigmalar kullanılarak farelerde Prosocial davranış analiz

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. ...

Assessment of Memory Function in Pilocarpine-induced Epileptic Mice

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal model of epilepsy, we generated pilocarpine-treated chronic epileptic mice. We present a protocol for three different behavioral tests using these epileptic mice: novel object location (NL), novel object recognition (NO), and pattern separation (PS) tests to evaluate learning and memory for places, objects, and contexts, respectively. We explain how to set the behavioral apparatus and provide experimental procedures for the NL, NO, and PS tests following an open field test that measures the animals&#8217; basal locomotor activities. We also describe the technical advantages of the NL, NO, and PS tests with respect to other behavioral tests for assessing memory function in epileptic mice. Finally, we discuss possible causes and solutions for epileptic mice failing to make 30 s of good contact with the objects during the familiarization sessions, which is a critical step for successful memory tests. Thus, this protocol provides detailed information about how to assess epilepsy-associated memory impairments using mice. The NL, NO, and PS tests are simple, efficient assays that are appropriate for the evaluation of different kinds of memory in epileptic mice.

This article presents experimental procedures for assessing memory impairments in pilocarpine-induced epileptic mice. This protocol can be used to study the pathophysiologic mechanisms of epilepsy-associated cognitive decline, which is one of the most common comorbidities in epilepsy.

Pilocarpine bağlı Epileptik Farelerde Hafıza Fonksiyonunun Değerlendirilmesi

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal ...

The Innovation Arena: A Method for Comparing Innovative Problem-Solving Across Groups

Problem-solving tasks are commonly used to investigate technical, innovative behavior but a comparison of this ability across a broad range of species is a challenging undertaking. Specific predispositions, such as the morphological toolkit of a species or exploration techniques, can substantially influence performance in such tasks, which makes direct comparisons difficult. The method presented here was developed to be more robust with regard to such species-specific differences: the Innovation Arena presents 20 different problem-solving tasks. All tasks are presented simultaneously. Subjects are confronted with the apparatus repeatedly, which allows a measurement of the emergence of innovations over time - an important next step for investigating how animals can adapt to changing environmental conditions through innovative behavior.
Each individual was tested with the apparatus until it ceased to discover solutions. After testing was concluded, we analyzed the video recordings and coded successful retrieval of rewards and multiple apparatus-directed behaviors. The latter were analyzed using a Principal Component Analysis and the resulting components were then included in a Generalized Linear Mixed Model together with session number and the group comparison of interest to predict the probability of success.
We used this approach in a first study to target the question of whether long-term captivity influences the problem-solving ability of a parrot species known for its innovative behavior: the Goffin&#180;s cockatoo. We found an effect in degree of motivation but no difference in the problem-solving ability between short- and long-term captive groups.

The Innovation Arena is a novel comparative method for studying technical innovation rate per time unit in animals. It is composed of 20 different problem-solving tasks, which are presented simultaneously. Innovations can be carried out freely and the setup is robust with regard to predispositions on an individual, population or species level.

İnovasyon Arenası: Gruplar Arasında Yenilikçi Problem Çözmeyi Karşılaştırmak İçin Bir Yöntem

Problem-solving tasks are commonly used to investigate technical, innovative behavior but a comparison of this ability across a broad range of species is ...

Assessment of Mouse Judgment Bias through an Olfactory Digging Task

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This phenomenon has long been observed in humans, with individuals in positive states responding to ambiguity 'optimistically' and those in negative states instead showing 'pessimism'. Researchers aiming to assess animal affect have taken advantage of these differential responses, developing tasks to assess judgment bias as an indicator of affective state. These tasks are becoming increasingly popular across diverse species and fields of research. However, for laboratory mice, the most widely used vertebrates in research and a species heavily relied upon to model affective disorders, only one JB task has been successfully validated as sensitive to changes in affective state. Here, we provide a detailed description of this novel murine JB task, and evidence of its sensitivity to mouse affect. Though refinements are still necessary, assessment of mouse JB opens the door for answering both practical questions regarding mouse welfare, and fundamental questions about the impact of affective state in translational research.

This article provides a detailed description of a novel mouse judgment bias protocol. Evidence of this olfactory digging task's sensitivity to affective state is also demonstrated and its utility across diverse research fields is discussed.

Koku Alma Kazma Görevi Yoluyla Fare Yargısı Önyargısının Değerlendirilmesi

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This ...

Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice

Long-lasting changes in the brain or &#8216;brain plasticity&#8217; underlie adaptive behavior and brain repair following disease or injury. Furthermore, interactions with our environment can induce brain plasticity. Increasingly, research is trying to identify which environments stimulate brain plasticity beneficial for treating brain and behavioral disorders. Two environmental manipulations are described which increase or decrease the number of tyrosine hydroxylase immunopositive (TH+, the rate-limiting enzyme in dopamine (DA) synthesis) neurons in the adult mouse midbrain. The first comprises pairing male and female mice together continuously for 1 week, which increases midbrain TH+ neurons by approximately 12% in males, but decreases midbrain TH+ neurons by approximately 12% in females. The second comprises housing mice continuously for 2 weeks in &#8216;enriched environments&#8217; (EE) containing running wheels, toys, ropes, nesting material, etc., which increases midbrain TH+ neurons by approximately 14% in males. Additionally, a protocol is described for concurrently infusing drugs directly into the midbrain during these environmental manipulations to help identify mechanisms underlying environmentally-induced brain plasticity. For example, EE-induction of more midbrain TH+ neurons is abolished by concurrent blockade of synaptic input onto midbrain neurons. Together, these data indicate that information about the environment is relayed via synaptic input to midbrain neurons to switch on or off expression of &#8216;DA&#8217; genes. Thus, appropriate environmental stimulation, or drug targeting of the underlying mechanisms, might be helpful for treating brain and behavioral disorders associated with imbalances in midbrain DA (e.g. Parkinson&#8217;s disease, attention deficit and hyperactivity disorder, schizophrenia, and drug addiction).

This protocol describes two different environmental manipulations and a concurrent brain infusion protocol to study environmentally-induced brain changes underlying adaptive behavior and brain repair in adult mice.

Yetişkin Farelerde Orta beyin dopamin Nöronlar Sayısının Çevre Modülleri

Long-lasting changes in the brain or &#8216;brain plasticity&#8217; underlie adaptive behavior and brain repair following disease or injury. Furthermore, ...