The authors have no acknowledgements.

윤리 문 : 모든 절차는 시드니 대학의 동물 윤리위원회의 승인을 국민 건강과 호주 가이드 라인의 의학 연구위원회 (Medical Research Council)를 본했다. 절차는 대학 시드니의 보쉬 설치류 시설에서 양육 된 C57 / BL6J 마우스에서 수행되었다. 모든 마우스는 건조 식품과 물에 대한 광고 무제한으로 액세스 할 수있는 개별 환기 케이지에서 0600 시간에 조명 12 시간 명암주기에 21 ° C의 주변 온도에서 단일 적절하게 통풍이 방에 보관되었다. 늦은 임신 여성을 무작위로 표준 또는 환경 풍부한 주거 조건에 할당되었다. 1. 주택 (농축 레벨) : <ol><li> 4 늦은 임신 성인 여성 쥐를 얻습니다. 무작위로 표준 상태에 2를 지정하고 하나의 빨간색 마우스 이글루를 포함하는 깨끗한 표준 마우스 케이지 (전체 크기 391 X 199 X 160mm)로 각각 배치합니다. 농축 된 상태의 경우, REMA를 배치ining 하나의 깨끗한 쥐 크기의 케이지에 2 마우스 (전체 치수 X 404mm 462 X 403). </li><li> 농축 케이지에, 감각과 운동 자극을 증가하도록 설계 객체의 다양한 (예 : 실행 휠, 시각적 자극, 냄새가 좋은면 공, 벨크로 스트립)를 배치합니다. </li><li> 모든 2~3일 새장 안에 대한 이러한 객체를 이동; 파괴 된 그 어떤를 새로 고칩니다. </li><li> 그들이 제기 된 환경 조건과 일치 남녀 분리 하우징 후 21 일 출생, 섹스 동물과 장소에서 이유시. 풍부한 조건은 2 케이지 당 3 10 마우스 및 표준을위한 5 마우스 사이에 있다는 것을 확인합니다. 동물 성인 (나이 12-14 주)에 도달하면 행동 테스트를 개시합니다. </li></ol> 퍼즐 상자 2. 건설 <ol><li> 6 흰색 아크릴 조각 (또는 다른 비 다공성 물질) 확보 : 한 750 X 280mm, 두 280 X 250mm, 두 750 X 250mm, 하나의 150 X 280mm (그림 1 참조). </li><li> 40 X 40mm 광장 개방이 조각의 한면으로 잘라, 검은 색 아크릴의 한 조각 280 X 250mm를 얻습니다 (그림 1 참조). </li><li> 다음과 같이 퍼즐 상자를 조립 : 상자의 바닥과 750 X 280mm 조각을 사용하여 상자의 끝, 그리고 상자의 측면과 750 X 250mm 조각으로 280 X 250mm 조각을 사용합니다. </li><li> 상자의 바닥에 구멍 플러시 (대형 하나 하나의 작은)를 하나의 끝에서 상자에 150mm를 측정하고, 두 개의 구획으로 분할하도록 상자에서 아크릴의 검은 조각을 배치합니다. </li><li> 흰색 아크릴의 150 X 280mm 조각을 가지고 어두운 &quot;목표 상자&quot;챔버를 제공, 확인 완전히이 지역을 커버하고 상자의 작은 구획 위에 놓습니다. 경첩에 의해 주요 상자의 몸에 아크릴이 조각을 부착, 또는 완전히 행동​​ 테스트 중에 제거 할 자유 둡니다. </li><li> 아크릴 (세 4 × 120mm)의 3 개를 가지고 &quot;U-shap를 만들기 위해 가입ED &quot;채널. </li></ol><img alt="그림 1" fo:content-width="5in" src="/files/ftp_upload/52225/52225fig1highres.jpg" width="500" /> 그림 1 : 퍼즐 박스 작업의 개략도. 퍼즐 박스는 오픈 필드 영역 (600 × 280mm)와 모두 750 X 280mm를 측정 숨겨 목표 박스 영역 (150 X 280mm)로 구성된 아크릴 상자입니다. 두 영역을 분리하는 파티션 (회색) 내에서 40 X 40mm 개방은 동물 열기 필드에서 덮여 목표 상자 영역에 액세스 할 수 있습니다. 이 구멍은 시험이 진행됨에 따라 제거 점점 더 어려운 장애물로 차단됩니다. 동물들은 각각 세 개의 실험 조건에 대한 네 개의 폐색 상태로 구성된 5 일간 프로토콜을 겪는다. 퍼즐 박스 작업 3. 실행 <ol><li> 철저히 70 % 알코올로 퍼즐 상자를 청소합니다. 각 시험 동물 사이에이 단계를 반복합니다. </li><li> 목표 상자 아칸소에서 깨끗한 빨간색 마우스 이글루를 배치퍼즐 박스의 개, 그리고 목표 상자의 뚜껑을 교체합니다. </li><li> 테스트되고, 폐색 상태가 발생하면, 목표 박스 내의 출입구 방해를 배치 (도 2 참조). </li><li> 마우스가 목표 상자 지향 퍼즐 박스의 오픈 필드 섹션으로, 테스트 및 목표 상자에서 마지막 인 제되고 놓습니다. </li><li> 퍼즐 상자의 목표 박스 섹션을 입력 동물의 네 발에 걸리는 시간을 기록한다. </li><li> 동물 목표 박스를 입력하지 않으면 설정된 제한 시간 (표 1 참조)에 도달하면, 시험을 종료. </li><li> 시험이 끝나면, 퍼즐 박스에서 동물을 제거하고 다음 재판이 시작될 때까지 별도의 유지 케이지에 넣습니다. 각 동물에 대한 실험 사이에 60-180 초 격차를 유지합니다. </li><li> 각 동물의 경우, 네 개의 장애물 조건과 각 조건의 세 가지 시험으로, 시험의 연속 5 일 동안 하루에 세 가지 시험을 수행합니다. 세 번째 트라이소정의 폐색 상태를 알 항상 후속 일에 투여한다 (표 1 참조). </li></ol><img alt="표 1" fo:content-width="5in" src="/files/ftp_upload/52225/52225table1.jpg" width="500" /> 표 1 : 퍼즐 박스 작업의 계획. 퍼즐 박스 작업은 5 일 동안 실행, 4 폐쇄 상태로 구성된다. 세 제 나흘 각 시험 및 일째 하나가있다. 각 방해 조건은 세 가지 시험이있다; 언젠가 처음 두, 세 번째 날 직후. 장애물 조건의 첫 번째 재판이 기본 문제 해결 능력을 테스트하는 것을 목표로, 두 번째 시험은 작업 수집 및 강화를 검사, 세 번째 시험은 솔루션 보유 및 리콜에 대한 분석으로 사용됩니다. <img alt="그림 2" fo:content-width="6in" src="/files/ftp_upload/52225/52225fig2highres.jpg" width="600" /> 그림 2 : 방해퍼즐 상자 작업 내에서 이온 상태. 퍼즐 박스 무대와 본 연구에서 사용 방해 조건의 개략도. (A) 조건 0 (C0), 오픈 필드와 목표 박스 영역 사이의 출입구 내 장애물이없는 존재와. (B) 조건 1 (C1 ), 오픈 필드와 목표 박스 영역 사이의 출입구 내에서 &quot;U 모양&quot;채널 선물. (C) 채널이 깨끗한 침구 소재로 가득 조건 2 (C2),. (D) 조건 3 (C3 ), 오픈 필드와 목표 박스 영역 사이의 출입구 내에 존재하는 &quot;조직 플러그&quot;와. (E) 오픈 필드와 목표 상자 사이의 출입구 내에 존재 &quot;폼 플러그&quot;와 조건 4 (C4) 지역. 방법 및 그림 1에 따라 경기장의 크기입니다. 데이터 4. 해석 <ol><li> 시간 중 하나가 COM에 취한 데이터를 표현또는 null 시험의 수 (null의 동물이 지정된 제한 시간 내에 작업을 완료하지 않은 시험 포함) 재판을하는 것이 현명한 방법. </li><li> 간 주제 요인으로 폐쇄 형 / 상태 (C) 및 작업 번호 (T) 내 - 과목 요인과 (농축 대 기준) 농축 수준, 퍼즐 박스 내에서 성능에 주택 조건의 효과를 평가하기 위해 반복 측정 ANOVA를 사용하여 . </li></ol>

The authors declare they have no competing financial interests.

제시된 데이터는 퍼즐 상자 효과적으로 사용될 수 EE의 영향을 평가하는 것을 보여준다. 풍부한 환경에서 발생하는 마우스는 지속적으로 표준 실험실 조건에서 제기 동물보다이 행동 분석에서 방해 퍼즐을 해결하는 데 훨씬 더 적은 시간이 걸렸습니다. 또한,이 차이는 EE 태스크가 제시 한 문제에 대한 해결책을 강화하거나 유지하는 능력을 기준으로 동물의 기본 문제 해결 능력에 더 큰 영향력을...

환경 농축 (EE)은 일관 초래, 동물의 행동에 영향을 미치는 것으로 밝혀졌다 사회적 상호 작용, 운동 활동, 통상 표준 실험실 environment.EE 경험보다 더 감각 자극에 대한 증가 된 기회를 가진 동물을 제공하는 환경으로 정의 될 수있다 이러한 학습과 기억 작업의 스트레스와 불안 관련 활동 8-10의 감소, 성능 향상 등의 변경 8, 11, 모터 조정과 탐구 활동 (11), 중독성 물질에 산모 관리 (8)뿐만 아니라 저항의 변화를 조기에 발병 12 15. 또한, EE는 발병을 지연시키고 헌팅 1-4,16, 파킨슨 (17) 및 알츠하이머 병 (18)의 동물 모델에서 증상의 중증도를 감소, 신경 퇴행성 질환의 효과를 개선하기 위해 보여왔다. 이러한 변화는 고전EE는 뇌 전반에 걸쳐 유도하는 것으로 알려져 해부학 분자 변경에 관한 것이다. 개발의 초기 단계에서 풍부한 환경에서 자란 동물 9,2-22과 시냅스 밀도 23 분기 수지상 증가 뇌 무게와 대뇌 피질의 두께를 포함하는 신경 변경의 무수를 보여준다. EE는 레벨 가속 감각 25,26,28,29 개발, 니모닉 (30)뿐만 아니라, 모터 회로들 (31, 32)에 기여하는 것으로 나타났다 성장 인자 발현 9,24-30, 양쪽의 타이밍을 변경할 수있다. 계정에 개별 연구 9,24,27,30 내에서 사용되는 동물과 환경의 다른 유형을 고려하지 않고, EE의 영향을 조사 할 때 이전 작업은 시간 모순 된 연구 결과에서 밝혀졌다. 현재, 상이한 균주의 다양한 사양 EE 패러다임의 효과를 측정하는 데 사용될 수있는 단순하고 일관된 행동 태스크가 없다동물의 이거 야. 퍼즐 박스 작업은 동물의 기본 문제는 능력 (7)을 해결 결정하는 간단한 테스트로 설계되었다. 오픈 영역에 배치 동물 덮여 지역 / 쉼터를 액세스하기 위해 작은 구멍에 위치하고 물질을 방해 제거해야합니다. 각 피실험자 세 가지인지 적 속성을 평가하기 위해 동일한 장애물 세 실험을 설명한다. 첫 시도는 고유 또는 기본 문제 해결 능력의 기준 표시를 산출한다. 동일한 날에 실행 번째 시험은을 개선하고, 따라서 특정 장애물을 제거하기위한 전략을 강화하는 동물의 능력의 어떤 표시를 제공한다. 다음 날짜에 이루어진 세 번째 시험은 작업에 학습 솔루션을 유지하고 기억하는 주체의 능력에 대한 통찰력을 제공합니다. 동물이 &quot;방해 퍼즐&quot;을 해결하기위한 동기는 잠재적으로 변화 될 수있다들판을 방지하고 주변 환경 6,7 탐험 쉼터뿐만 아니라 고유의 드라이브를 추구하는 타고난 욕망을 불러 일으킨다. 퍼즐 상자를 해결하기 위해 욕망을 기본 잠재적 인 행동 드라이버의 다수는 뇌의 다양한 영역이 작업 성능을 중재에 참여하는 것이 좋습니다. 이전 연구는 정신 분열증의 쥐 모델에서, 전두엽 피질뿐만 아니라 해마가이 작업 (5)의 인수에 참여하는 것으로 나타났습니다. 쥐의 병변 연구는 또한 다양한 시상 핵, 시상 하부, 소뇌, 그리고 변연계 구조를 포함 퍼즐 박스 성능에 관련된 뇌 영역의 큰 숫자를 공개했다. 함께, 이러한 결과는 작업을 해결하는이 문제에 관여하는 것은인지 기능과 관련된 신경 구조의 호스트를 포함 나타냅니다. 퍼즐 상자 m에 의해 전시 된 쥐의 능력을 문제 해결뿐만 아니라인지 적자를 평가하기 위해 성공적으로 사용되어왔다정신 분열증 5-7의 소변 모델. 작업의 성능은 매우 일관성이 있어야하고, 다른인지 행동 검사 (6)의 결과와 상관 관계가 밝혀졌다. 이 연구의 목적은 EE의 유효성을 판정하는 간단하고 신뢰성있는 방법이 될 퍼즐 상자 태스크에 적응하는 것이였다.

<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.

여기에 설명 된 결과는 다른 새끼로 구성된 여러 동료에서 가져온 데이터, 대표 샘플입니다. 모든 행동 테스트는 코호트 내에서 동물의 무작위 시험 순서로, 0700 및 1100 시간 사이에 실시되었다. (15, 7 여성 8 남성 N = ()를 참조 풍부한 환경에서 자란 동물 (N = 14, 7 여성 7 남성) 표준 환경에서 제기보다 퍼즐 박스 내에서 방해 작업을 해결하기 위해 훨씬 적은 시간이 걸렸습니다 그림 3) (?...

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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.

보충 환경의 효능을 평가하는 수단으로서 퍼즐 상자의 사용

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

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JoVE Journal

Behavior

11.7K 조회수.  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.

비디오: 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.

수정 된 구멍 보드 - 마우스 및 쥐의 행동,인지 및 사회적 상호 작용을 측정

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

연구

행동분석학

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.

풍부한 환경에서의 주택 마우스를위한 프로토콜

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.

평가는 마우스에 둥지 건설, 그리고 비장을내는

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

신경과학

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.

마우스의 높은 주문 반복적 인 행동에 대한 잠재적 인 분석으로 소설 개체 탐사

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.

실험실 쥐에 대한인지 심화로 리모콘 교육 소개

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.

공간 학습 및 반 즈 미로 계 집 아이-에서-조 난 패러다임을 사용 하 여 마우스 Prosocial 동작 분석

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

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

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive decline, such as Alzheimer&#39;s disease (AD), have become a promising tool to elucidate the underlying mechanisms and promote the therapeutic advances. An important step is the validation and characterization of expected behavioral abnormality in the models, in the case of AD, cognitive decline. The long-term behavioral investigations of laboratory animals to study the effect of aging demand substantial efforts from researchers. The IntelliCage system is a high-throughput and cost-effective test battery for mice that eliminates the need for daily human handling. Here, we describe how the system is utilized in the long-term phenotyping of a genetic Alzheimer&#39;s disease model, specifically focusing on the cognitive functions. The experiment employs repeated battery of tests that assess spatial learning and executive functions. This cost-effective age-dependent phenotyping allows us to identify the transient and/or permanent effects of genes on various cognitive aspects.

This paper describes a protocol for cognitive assessments for genetic models of the Alzheimer&#39;s disease using the IntelliCage system, which is a high throughput automated behavioral monitoring system with operant conditioning.

자동화, Alzheimer의 질병, IntelliCage를 사용 하 여 여러 유전자 모델에서 인지 기능에 대 한 장기적인 행동 분석 결과

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

Simultaneous Monitoring of Wireless Electrophysiology and Memory Behavioral Test as a Tool to Study Hippocampal Neurogenesis

Brainwaves amplitude obtained from electroencephalography (EEG) has been well-recognized as a basis for cognitive capacity, memory, and learning on animals and humans. Adult neurogenesis mechanism is also linked to memory and learning improvement. Traditionally, researchers used to assess learning and memory parameters in rodent models by behavioral tasks. Therefore, the simultaneous monitoring of behavioral changes and EEG is particularly interesting in correlating data between brain activity and task-related behaviors. However, most of the equipment required to perform both studies are either complex, expensive, or uses a wired setup network that hinders the natural animals&#8217; movement. In this study, EEG was recorded with a wireless electrophysiology device along with the execution of a novel object recognition task (NORT). The animal&#8217;s behavior was monitored simultaneously by a video tracking system. Both recordings were analyzed offline by their timestamps which were synched to link EEG signals with the animal&#8217;s actions. Subjects consist of adult Wistar rats after medium-term environmental enrichment treatment. Six skull screw electrodes were fixed in pairs on both hemispheres over frontal, central, and parietal regions and were referenced to an electrode located posterior of the nasal bone. NORT protocol consists of exposing the animal to two identical objects for 10 min. After 2 h and 24 h, one of the objects was replaced with a novel one. Exploration time for each object was monitored by a behavioral tracking software (BTS) and EEG data recording. The analysis of the EEG synced with behavioral data consists of estimations of alpha and beta relative band power and comparisons between novel object recognition versus familiar object exploration, between three experimental stages. In this manuscript, we have discussed electrodes manufacturing process, epidural electrodes implantation surgery, environmental enrichment protocol, NORT protocol, BTS setup, EEG &#8211; BTS coupling for simultaneous monitoring in real-time, and EEG data analysis based on automatic events detection.

The protocol presented here provides information on the simultaneous electroencephalography (EEG) and behavioral assessment in real-time. We have discussed all steps involved in this protocol as an attractive solution for researchers in many fields of neuroscience, particularly in learning and memory areas.

해마 신경 발생을 연구하기 위한 도구로서의 무선 전기생리학 및 기억 행동 테스트의 동시 모니터링

Brainwaves amplitude obtained from electroencephalography (EEG) has been well-recognized as a basis for cognitive capacity, memory, and learning on ...

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.

혁신 경기장 : 그룹 간 혁신적인 문제 해결을 비교하는 방법

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.

후각 파기 작업을 통한 마우스 판단 편향 평가

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