Name: introducing clicker training as a cognitive enrichment for laboratory mice
Uploaded: 2017-03-06T15:00:00.000+00:00
Duration: 5 min 33 s
Description: Watch this Scientific Journal Video about Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice at JoVE.com

This work was supported by the Translational Animal Research Center of the University Medical Center of the Johannes Gutenberg-University Mainz. The authors are most grateful to Thomas Wacker for his technical support.

윤리 정책 : 마우스와 실험 절차의 처리는 국가 유럽, 및 동물 보호를위한 제도적 지침에 따라 실시 하였다. 참고 :이 프로토콜은 주말 (토요일과 일요일)에 휴식과, 개입 5 일 (월요일 ~ 금요일)을 포함한다. 프로토콜은 쉽게 특정 요구를 만족하도록 구성 될 수있다. 1. 두 번째 보강제로서 적절한 보상을 결정 참고 : 진공 포장 된 식품 또는 식품 안전 기준을 충족 동물 사료로 사용 식품 보상. 예를 들어, 견과류, 초콜릿, 젤리 곰, 또는 말린 과일의 종류가 적합하다. <ol><li> 다른 음식 보상 홈 케이지로 (그림 1) (0.5 cm 3 개)와 작은 페트리 접시를 삽입합니다. </li><li> 10 분 후, 먹다 남은 음식을 확인합니다. </li><li> 모든 보상은 10 분 후에 먹을 경우 선호도를 추정 할 수있을 때까지의 시간 간격을 단축. </li><li> 날 (4, 5) (예 Thursday를 금요일), 보상에 새장의 모든 마우스의 허식을 설정하는 홈 케이지에 대한 선호 ( &quot;승자&quot;) 보상의 소량을 추가합니다. </li><li> 마우스가 마우스 터널에 길들여 있지 않은 경우 (최소 2 일 주말에 예를 들면 교육, 시작하기 전에) 케이지에 터널을 추가합니다. </li><li> 반복 1.2 단계 - 1.4 3 일 연속 (수요일 예를 들어, 월). </li></ol> 2. 리모콘 교육 <ol><li> 각 교육 세션에 대한 준비 참고 : 마우스는이 프로토콜에서 해제해야 할 때마다, 조용하고 부드러운 방법으로 올립니다. 들어 올려 마우스에서 손을 넣습니다. 처음 몇 시간 동안, 마우스는 교반 할 수 있지만, 습관화 처리가 며칠 후에 완료된다. 이 단계는 어려움을 작성하는 경우, 28 &quot;오픈 손에 넣는&quot;에 대한 프로토콜을 참조하는 것이 유용하다. <ol><li> 침구 소재와 케이지를 준비합니다. </li><li> 트라nsfer 마우스 케이지는 조용한 장소로 훈련된다. </li><li> 보상을 준비하고 타이머 및 준비 리모콘 / 대상 스틱 조합이있다. 주 : 생쥐 처리에 순응 이미 실험자와 신뢰 관계를 가질 경우, 마우스를 수동으로 공급 될 수있다. 그렇지 않은 경우, 마우스는 실험에서의 거리를 유지할 수있는 방법으로 스틱 또는 집게로 보상을 첨부. </li><li> 이제 교육 영역의 역할을 가정 케이지에서 모든 개체를 제거합니다 (등 예를 들어, 마우스 주택, 둥지 - 건축 자재를.). </li><li> 준비된 케이지 케이지 일행을 전송합니다. </li></ol></li><li> 모든 교육 세션에 적용되는 일반 규칙 참고 : 다음과 같은 일반적인 규칙은 모든 세션에 적용하고 프로토콜을 통해 다시 언급되지 않습니다. <ol><li> 5 분마다 마우스를 양성. 30의 훈련과 15의 휴식 기간 사이의 대체. </li><li> 마우스가 두 번째보다 더 이상 보상에 갉아 먹다 할 수 없습니다. 그런 다음, 케이지에서 (보상과) 스틱을. </li><li> 보람의 다음과 같은 패턴을 실행합니다 : 1 - 행동의 10 공연 : 모든 시간을 보상. (11) - 행동 (21) 성능 : 매 초마다 시간을 보상. 에 행동의 22 성능에서 : 매 세 번째 시간을 보상. </li><li> 교육의 4 분 후, 원하는 동작의 다음 공연은 대성공 보상에 의해 강화된다. 마우스가 세 번 이상 이전보다 음식 보상에 갉아 먹다 할 수 있습니다. </li></ol></li><li> 교육 세션 1 일 : &quot;음식 보상과 보조 보강재를 연결&quot; <ol><li> 5 분, 프레스 시작 타이머를 설정하고 홈 케이지에 마우스 터널을 추가 할 수 있습니다. 참고 : 마우스의 타고난 thigmotaxis을 활용 옆 벽 (그림 2)에 터널을 배치합니다. 처음 몇 개의 세션이 터널에 진입 마우스의 가능성을 향상시킬 것이다. </li><li> 마우스가 터널을 검사 할 때까지 기다립니다. 즉시 MOUS로전자는 클릭하고 터널의 끝에서 보상을 제시 터널로 들어갑니다. </li><li> 터널에 앉아있는 동안 보상에 마우스 피드를 보자. </li><li> 마우스가 터널에 앉아있는 동안 15 초 동안 계속 클릭합니다. </li><li> 즉시 마우스가 터널을 떠날 때, 3.2 단계로 돌아갑니다. </li></ol></li><li> 교육 세션 일 2-5 : &quot;터널을 통해 실행&quot; <ol><li> 5 분, 프레스 시작 타이머를 설정하고 홈 케이지에 마우스 터널을 추가 할 수 있습니다. </li><li> 즉시 마우스 터널 진입로 클릭하고 터널의 끝에서 보상을 제시한다. </li><li> 한 마우스 터널처럼, 클릭 바로 동일한 방식으로 상을 제시한다. </li><li> 다음 30 초 동안이 과정을 반복하고, 15 초는 새장 밖으로 터널을 적용하려면 다음 일시 중지합니다. </li><li> 다시 터널을 추가하고 마우스가 터널 재진입 할 ​​때 즉시 클릭합니다. </li><li> 터널의 끝에서 보상을 제시한다. </li><li> 마우스가 1 초 동안 갉아 먹다 할 수 있습니다. </li&gt; <li> 보상을 빼앗아. </li><li> 즉시 마우스가 시작 다시 입력으로 자체 터널, 터널 (그림 3)의 끝 부분의 앞의 상을 제시한다. </li></ol></li><li> 교육 세션 주 2 : &quot;대상 스틱에 따라&quot; <ol><li> 5 분, 프레스 시작 타이머를 설정하고 케이지의 대상 스틱의 끝에서 세계를 놓습니다. </li><li> 즉시 마우스가 세계에 관심을 같이 클릭하고 세계 옆에 보상을 제시 (그림 4, 5). </li><li> 그것의 코를 가진 세계를 접촉 후에 마우스를 보상. </li><li> 마우스가 보상에 수행 된 조치를 연결하면, 교육 세션 (그림 6) 동안 전 세계의 위치를 변경합니다. </li><li> 이 마지막 과제를 해결하기 위해 마우스 기다립니다. </li><li> 케이지에서 세계를 놓습니다. </li><li> 마우스가 세계를 감동 직전, 차분히 1cm에 의해 세계의 위치를 ​​변경합니다. </l난&gt; <li> 클릭하고 마우스가 거리를 건너 세계에 닿을 경우 보상. </li><li> 마우스가 확실하게 다음 때까지이 절차를 반복합니다. </li><li> 천천히 마우스가 교차하는 거리를 확장 할 수 있습니다. </li></ol></li><li> 교육 세션 주 3 : &quot;실험자의 손에 대상 스틱에 따라&quot; <ol><li> 리모콘 / 대상 스틱 조합 및 다른 손으로 보상을 누른 상태에서 훈련 케이지에 한 손을 놓습니다. </li><li> 5 분, 프레스 시작 타이머를 설정하고 손 옆 대상 스틱의 끝에서 세계를 놓습니다. </li><li> 즉시 마우스가 세계에 관심을 같이 클릭하고 세계 옆에 보상을 제시한다. </li><li> 즉시 마우스가이 도전을 충족로 가까이 손에 세계 여러 단계를 이동합니다. </li><li> 손의 손바닥에 세계를 놓습니다. 클릭하고 마우스가 손의 손바닥 (그림 7)에 앉아있는 동안 보상. </li></ol></li></ol>

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L., West, R. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Taming+anxiety+in+laboratory+mice.">Taming anxiety in laboratory mice.</a> Nature Methods. 7 (10), 825-826 (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=.">.</a> What's Wrong With My Mouse?. , (2007).</li><li>Loos, M., Koopmans, B., 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=Within-strain+variation+in+behavior+differs+consistently+between+common+inbred+strains+of+mice.">Within-strain variation in behavior differs consistently between common inbred strains of mice.</a> Mammalian genome : official journal of the International Mammalian Genome Society. 26 (7-8), 348-354 (2015).</li><li>Seibenhener, M. L., Wooten, M. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+the+Open+Field+Maze+to+Measure+Locomotor+and+Anxiety-like+Behavior+in+Mice.">Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice.</a> Journal of visualized experiments : JoVE. (96), e1-e6 (2015).</li><li>Can, A., Dao, D. T., Arad, M., Terrillion, C. E., Piantadosi, S. C., Gould, T. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Mouse+Forced+Swim+Test.">The Mouse Forced Swim Test.</a> Journal of Visualized Experiments. , 4-8 (2011).</li><li>Clayton, L. A., Tynes, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Keeping+the+Exotic+Pet+Mentally+Healthy.">Keeping the Exotic Pet Mentally Healthy.</a> Veterinary Clinics of North America: Exotic Animal Practice. 18 (2), 187-195 (2015).</li><li>Ward, S. J., Melfi, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+implications+of+husbandry+training+on+zoo+animal+response+rates.">The implications of husbandry training on zoo animal response rates.</a> Applied Animal Behaviour Science. 147 (1-2), 179-185 (2013).</li></ol>

The authors have nothing to disclose.

각각의 섹스 (12) BALB / C 근친 마우스의 코호트와 리모콘 훈련 프로토콜의 효과적인 구현은 복잡하지 않은 것으로 판명. 이전 연구는 여러 종과 식자 교육의 효과를 확인했다, 우리는 마우스에이 확장. 쥐 실험 동물 중 가장 낮은 개발 포유류로, 자신의 능력은 종종 과소 평가된다. 따라서, 상기 데이터의 가장 놀라운 양태는 훈련 성공 거의 모든 마우스에 의해 달성 될 수있다. ...

실험실 쥐에 대한 새로운 정제 전략의 개발은 실험실 동물 과학 (1) 상기 3RS의 이행 (교체, 감소 및 정제)에 기여하는 어려운 작업입니다. 정제 분야의 개선은 추가적인 실험을 위해 사용되는 동물의 수백만의 복지에 기여할 수있다. 따라서, 집중 연구 분야에서 필요하다. 이것은 또한 유럽 연합 (EU)의 지침 63분의 2,010의 정의 된 목표이다. 지침 63분의 2,010 / EU는 실험 동물의 수명 경험을 강화해야한다는 지적과 (제 3.7) 2 &quot;시설이 습관화 및 교육 동물에 적합한 프로그램, 절차 및 프로젝트의 길이를 설정해야한다&quot;고. 그들이 보관하고 실험을 위해 사육되는 동안 실험 동물은 많은 스트레스 상황을 경험할 수 있습니다. 노동 사이 보통 상호atory 마우스와 책임있는 사람들은 오히려 제한됩니다. 따라서, 신뢰 관계가 발전 할 수 없습니다. 이 동물들 3, 4, 5, 6의 동작 생리학, 따라서 복지에 해로운 취급 반응에서 증가 된 불안과 스트레스를 유발할 수있다. 또한, 정기적으로 스트레스 호르몬이나 행동 7, 8 등 다양한 매개 변수를 측정하여 검사 할 수 스트레스 반응을 일으킬 수 일반적인 처리, 억제, 혈액 또는 조직 샘플링 같은 실험 절차를 수행. 이 처리 프로그램을 효율적 실험실 설치류 9, 10, 11 연구자 향해 불안을 감소시킬 수 있음을 보여왔다. 따라서 동물 &#39;을 향상시킬 수 처리 프로그램조건은 동물 복지 5에 크게 기여할 수있다. 이 연구의 목적은 특정 처리 프로그램으로 마우스에 대한 긍정적 인 강화 훈련을 소개하는 것입니다. 긍정적 인 강화 훈련은 연구자에게 동물의 행동을 형성 할 수있는 수단을 제공 조건화의 한 형태이다. 동물이 원하는 동작을 수행 할 때, 그것은 (여기서, 음식 보상) 양 자극 따른다. 목적은 동물이 각각의 행동에 대한 보상을 연결하는 것입니다. 리모콘 훈련은, ㄱ 리모콘의 소리를 &quot;클릭&quot;컨디셔닝 차 보강재를 사용하여 긍정적 인 강화 훈련의 한 형태이며, 특정 행동 (12)을 강화하기 위해 입증되었습니다. 보다 구체적으로, 클릭 음이 동작하고 곧 보상 (13) 사이에 &quot;시간 브릿지&quot;로 기능한다. 동물이 원하는 수행 정확하게 할 때 트레이너 클릭문제는, 어떤 시간없이 14을 지연 한 다음 음식 보상을 제공합니다. 이 높은 주파수로 수행 될 보상 동작을 강화한다. 리모콘 훈련은 널리 반려 동물과 함께 사용되며 성공적 인간이 아닌 영장류 13, 15, 16로 구현 된 실험 동물 과학에 그것의 방법을했다. 조건화 패러다임에 도전 할 때 마우스를 신속 오히려 배우로서, 두 번째 보강제의 도입은인지 능력 5, 17, 18, 19를 너무 긴장하지 않아야합니다. 마우스의 유지에 리모콘 교육을 도입함으로써, 우리는인지 농축을 경험 쥐를 할 수 있습니다. 인지 농축의 디자인은 SOLV 자신의인지 능력을 사용하도록 마우스를 사용하도록 설정해야합니다전자의 문제는 환경 (20), (21)을 통해 제어 할 수 있습니다. 다른 종과 여러 연구 포로 동물 22, 23, 24의 복지에인지 농축의 긍정적 인 영향을 증명한다. 성공적으로 환경 문제에 대처하기위한 동물의 능력을 강화하여 그 25 26 복지에 기여한다. 동물이 평생 동안 스트레스의 낮은 수준을 발생하는 경우 또한, 그들은 생물 의학 연구에서 발생하는 스트레스에 직면 해로운 대처 전략을 개발하는 적은 경향이있다. 따라서,인지 농축 일관된 구현은 피험자의 표현형의 균일화에 기여할 수있다. 이 필요한 환자의 수를 줄일 수 있기 때문에 이것은 감소의 3R 원리에 기여통계 요구 사항 (27)을 충족합니다. 쉽게 실험실 쥐를 유지의 일상 생활에 통합 할 수있는 신뢰할 수있는 프로토콜을 개발함으로써, 우리는 실질적으로 복지의 수명 경험을 향상시킬 수 있습니다.

<table><tbody><tr><td>Lid for open housing</td><td>Tecniplast</td><td>GM500LID117</td><td></td></tr><tr><td>SealSAfe Plus top for open housing</td><td>Tecniplast</td><td>GM500400SU</td><td></td></tr><tr><td>Type II long, filter top cages</td><td>Tecniplast</td><td>GM500PFSPC</td><td></td></tr><tr><td>Aspen bedding material&amp;nbsp;</td><td>Lab &amp;amp; Vet Service GmbH</td><td>H0234-300</td><td>Environmental enrichment</td></tr><tr><td>Red polycarbonate Mouse House</td><td>Tecniplast</td><td>ACRE011</td><td>Environmental enrichment</td></tr><tr><td>Tissue papers</td><td>Tork, SCA Hygiene Products GmbH</td><td>290179</td><td>Environmental enrichment</td></tr><tr><td>Food - ssniff M-H Extrudat</td><td>ssniff</td><td>V1126-000</td><td>ad libitum</td></tr><tr><td>Target Stick with Clicker</td><td>Trixie</td><td>2282</td><td></td></tr><tr><td>PVC Tube (Tunnels)&amp;nbsp;</td><td>Thyssen Krupp</td><td>RTPVCU04003005</td><td></td></tr><tr><td>White Chocolate/ white chocolate cream</td><td></td><td></td><td>Company doesn&#039;t matter, preferable organic quality</td></tr><tr><td>Forceps</td><td>FineScienceTools</td><td>&lt;em&gt;e.g.&lt;/em&gt; 11150-10</td><td>Or any other tool to fixate chocolate</td></tr><tr><td>Prism Version 6.0 for Windows&amp;nbsp;</td><td>GraphPad Software</td><td></td><td></td></tr></tbody></table>

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.

가장 중요한 단계의 첫번째와 하나가 적절한 음식 보상의 결정이었다. 따라서, 마우스는 페트리 접시 (도 1)에 너트 당 용액, 잼, 초콜릿의 다른 종류의 여러 가지 제안 하였다. 우리의 경험에서, 마우스는 화이트 초콜릿에 대한 분명한 선호도를 보였다. 따라서, 우리는 더 교육 프로세스에 화이트 초콜릿을 사용했다. <p class="jove_content" fo:keep-together.within-page=...

Watch this Scientific Journal Video about Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice at JoVE.com

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

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 ...

introducing-clicker-training-as-cognitive-enrichment-for-laboratory

Research

JoVE Journal

Behavior

12.8K 조회수.  Johannes Gutenberg-Universität Mainz. 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. 

비디오: Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

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.

마우스의 자동화, 정량인지 / 행동 검사 : 유전학, 약리학, 동물인지 및 학부 교육을위한

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

연구

행동분석학

A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. Higher cognitive functions that require precise control over sensorimotor responses such as decision-making and attentional modulation, however, are typically assessed in nonhuman primates. Despite the richness of primate behavior that allows multiple variants of these functions to be studied, the rodent model remains an attractive, cost-effective alternative to primate models. Furthermore, the ability to fully automate operant conditioning in rodents adds unique advantages over the labor intensive training of nonhuman primates while studying a broad range of these complex functions.
Here, we introduce a protocol for operantly conditioning rats on performing working memory tasks. During critical epochs of the task, the protocol ensures that the animal's overt movement is minimized by requiring the animal to 'fixate' until a Go cue is delivered, akin to nonhuman primate experimental design. A simple two alternative forced choice task is implemented to demonstrate the performance. We discuss the application of this paradigm to other tasks.

A fully automated protocol for rodent operant conditioning is proposed. The protocol relies on precise temporal control of behavioral events to investigate the extent to which this control influences neural activity underlying sensorimotor integration and cognitive control experiments.

감각 운동 통합 및인지 제어 실험을 위해 완전 자동화 된 설치류 컨디셔닝 프로토콜

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. ...

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain&#160;to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.

The goal of this protocol is to perform a behavioral assay such as the attentional set shifting task (AST) to assess prefrontal cortex-mediated cognitive flexibility in mice.

주의력 설정 쉬프트 작업 : 마우스의인지 적 유연성의 측정

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

Operant Sensation Seeking in the Mouse

Operant methods are powerful behavioral tools for the study of motivated behavior. These 'self-administration' methods have been used extensively in drug addiction research due to their high construct validity. Operant studies provide researchers a tool for preclinical investigation of several aspects of the addiction process. For example, mechanisms of acute reinforcement (both drug and non-drug) can be tested using pharmacological or genetic tools to determine the ability of a molecular target to influence self-administration behavior1-6. Additionally, drug or food seeking behaviors can be studied in the absence of the primary reinforcer, and the ability of pharmacological compounds to disrupt this process is a preclinical model for discovery of molecular targets and compounds that may be useful for the treatment of addiction3,7-9. One problem with performing intravenous drug self-administration studies in the mouse is the technical difficulty of maintaining catheter patency. Attrition rates in these experiments are high and can reach 40% or higher10-15. Another general problem with drug self-administration is discerning which pharmacologically-induced effects of the reinforcer produce specific behaviors. For example, measurement of the reinforcing and neurological effects of psychostimulants can be confounded by their psychomotor effects. Operant methods using food reinforcement can avoid these pitfalls, although their utility in studying drug addiction is limited by the fact that some manipulations that alter drug self-administration have a minimal impact on food self-administration. For example, mesolimbic dopamine lesion or knockout of the D1 dopamine receptor reduce cocaine self-administration without having a significant impact on food self-administration 12,16. 
Sensory stimuli have been described for their ability to support operant responding as primary reinforcers (i.e. not conditioned reinforcers)17-22. Auditory and visual stimuli are self-administered by several species18,21,23, although surprisingly little is known about the neural mechanisms underlying this reinforcement. The operant sensation seeking (OSS) model is a robust model for obtaining sensory self-administration in the mouse, allowing the study of neural mechanisms important in sensory reinforcement24. An additional advantage of OSS is the ability to screen mutant mice for differences in operant behavior that may be relevant to addiction. We have reported that dopamine D1 receptor knockout mice, previously shown to be deficient in psychostimulant self-administration, also fail to acquire OSS24. This is a unique finding in that these mice are capable of learning an operant task when food is used as a reinforcer. While operant studies using food reinforcement can be useful in the study of general motivated behavior and the mechanisms underlying food reinforcement, as mentioned above, these studies are limited in their application to studying molecular mechanisms of drug addiction. Thus, there may be similar neural substrates mediating sensory and psychostimulant reinforcement that are distinct from food reinforcement, which would make OSS a particularly attractive model for the study of drug addiction processes. The degree of overlap between other molecular targets of OSS and drug reinforcers is unclear, but is a topic that we are currently pursuing. While some aspects of addiction such as resistance to extinction may be observed with OSS, we have found that escalation 25 is not observed in this model24. Interestingly, escalation of intake and some other aspects of addiction are observed with self-administration of sucrose26. Thus, when non-drug operant procedures are desired to study addiction-related processes, food or sensory reinforcers can be chosen to best fit the particular question being asked. 
In conclusion, both food self-administration and OSS in the mouse have the advantage of not requiring an intravenous catheter, which allows a higher throughput means to study the effects of pharmacological or genetic manipulation of neural targets involved in motivation. While operant testing using food as a reinforcer is particularly useful in the study of the regulation of food intake, OSS is particularly apt for studying reinforcement mechanisms of sensory stimuli and may have broad applicability to novelty seeking and addiction.

In this protocol we describe a method of operant learning using sensory stimuli as a reinforcer in the mouse. It requires no prior training or food restriction, and it allows the study of motivated behavior without the use of a pharmacological or natural reinforcer such as food.

마우스의 추구 Operant 감각

Operant methods are powerful behavioral tools for the study of motivated behavior.  These 'self-administration' methods have been used extensively in drug ...

신경과학

Quantifying Social Motivation in Mice Using Operant Conditioning

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.

This article describes a new protocol for the quantitative measurement of social motivation in mice using operant conditioning for a social reward. The protocol is useful for the measurement of social motivation in mouse models of autism and other disorders of social behavior.

조건화를 사용하여 마우스 사회적 동기 부여를 정량화

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered ...

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.

여러인지 기능을 테스트 및 설치류에의 연결 활동을 녹음하기위한 완전 자동화된 고도 다목적 시스템

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

Using Clicker Training and Social Observation to Teach Rats to Voluntarily Change Cages

Cage cleaning is a routinely performed husbandry procedure and is known to induce stress in laboratory rats. As stress can have a negative impact on well-being and can affect the comparability and reproducibility of research results, the amount of stress experienced by laboratory animals should be minimized and avoided when possible. Further, the direct contact between the rat and animal caretaker during the cage change bears hygiene risks and therefore possibly negatively impacts the well-being of the rats and the quality of the research. 
Our protocol aims to improve the routinely performed cage changing procedure. For this reason, we present a feasible protocol that enables rats to learn via clicker training and observation to voluntarily change to a clean cage. This training helps to reduce stress caused by the physical disturbance and handling associated with the cage changes and concurrently enables a reduction in direct contact between animal and animal caretaker after the training phase is completed.
The implementation of clicker training to rats is fast and easy. Rats are generally interested in the training and efficiently learn the desired behavior, which entails changing cages through a pipe. Even without training, the rats learn to perform the desired behavior by observation, as 80% of the observational learning group successfully changed cages when tested. The training further helps to establish a relationship of trust between trainer and animal. As hygiene and well-being are both very important in animal experiments, this protocol might also help to improve high-quality research.

This protocol introduces a method of cage change for rats via clicker training. Rats learn the desired behavior not only by direct training but also by observational learning. The implementation of this fast and easy protocol might help to improve well-being and hygiene in rodent facilities.

자발적으로 감 금 소를 변경 하는 쥐 가르치는 식자 교육 및 사회적 관찰을 사용 하 여

Cage cleaning is a routinely performed husbandry procedure and is known to induce stress in laboratory rats. As stress can have a negative impact on ...

Evaluating Skilled Prehension in Mice Using an Auto-Trainer

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that permits the mouse to reach out of its cage and retrieve food pellets. Minimal food restriction is employed to encourage the mice to perform the food retrieval from the slot. As the mice begin to associate coming to the slot for food, the pellets are manually pulled away to stimulate extension and pronation of their paw to grasp and retrieve the pellet through the frontal slot. When the mice begin to reach for the pellets as they arrive at the slot, the behavioral assay can be performed by measuring the rate at which they successfully grasp and retrieve the desired pellet. They are then introduced to an auto-trainer that automates both the process of providing food pellets for the mouse to grasp, and the recording of successful and failed reaching and grasping attempts. This allows for the collection of reaching data for multiple mice with minimal effort, to be used in experimental analysis as appropriate.

Method to assess the impact of training on motor skills is a useful tool. Unfortunately, most behavioral assessments can be labor intensive and/or expensive.We describe here a robotic method of assessing prehension (reach-to-grasp) skill in mice.

자동 트레이너를 사용하여 마우스에서 숙련된 사전 평가

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that ...

일상적인 토끼 사육 절차를 위한 긍정적 강화 기반 교육

Training Laboratory Rabbits to Refine Routine Husbandry Procedures

Non-aversive handling and training techniques for laboratory animals are required to facilitate experimental and routine husbandry procedures, improving both animal welfare and scientific quality. Clicker training was utilized to develop training protocols for rabbits to refine stressful routine husbandry procedures usually associated with lifting (i.e., being picked up from the floor)/restraining (i.e., being held in the arms of a human) them. Thirteen female New Zealand White rabbits were trained over three weeks. All rabbits learned the predefined goal behaviors: they followed the target stick, jumped onto the weighing scale, entered a transport box, and reared while placing their front paws onto the trainer&#39;s hand. In addition, ten animals jumped from the floor onto the sitting trainer&#39;s lap and allowed the trainer to lift their paws off the surface while sitting on the trainer&#39;s lap. For some individuals, the protocols had to be adapted by additional interim steps. At the end of the training, the rabbits reliably showed the expected goal behaviors, even after short and long training breaks. With few exceptions, a familiar person other than the trainer could elicit the goal behaviors from the rabbits (generalization), though further sessions were required for generalization. In the voluntary approach test, the rabbits preferred interacting with the trainer in the 1st trial but spent as much time with an unfamiliar person as with the trainer in the 2nd trial. The behavioral observations suggested that picking the rabbits up with the transport box, as described in the protocol, instead of restraining them with the scruff of their neck and lifting them on the arm, was less aversive. All in all, the training protocols were feasible and can serve as a refinement strategy in laboratory animal facilities. In the interest of animal welfare, the training protocols should be applied wherever possible.

저자 스포트라이트: 부드럽고 스트레스 없는 취급을 위한 실험실 동물 훈련

Training protocols involving positive reinforcement for routine husbandry procedures in rabbits were developed and proved to be successful, as the rabbits reliably showed the trained behaviors at the weekly general examination. Picking the rabbits up with the transport box was less aversive than the conventional handling technique.

일상적인 사육 절차를 개선하기 위해 실험실 토끼 훈련

Non-aversive handling and training techniques for laboratory animals are required to facilitate experimental and routine husbandry procedures, improving ...

실험실 쥐에 대한인지 심화로 리모콘 교육 소개

요약

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이 비디오의 챕터

마우스의 자동화, 정량인지 / 행동 검사 : 유전학, 약리학, 동물인지 및 학부 교육을위한

감각 운동 통합 및인지 제어 실험을 위해 완전 자동화 된 설치류 컨디셔닝 프로토콜

주의력 설정 쉬프트 작업 : 마우스의인지 적 유연성의 측정

마우스의 추구 Operant 감각

조건화를 사용하여 마우스 사회적 동기 부여를 정량화

여러인지 기능을 테스트 및 설치류에의 연결 활동을 녹음하기위한 완전 자동화된 고도 다목적 시스템

자발적으로 감 금 소를 변경 하는 쥐 가르치는 식자 교육 및 사회적 관찰을 사용 하 여

자동 트레이너를 사용하여 마우스에서 숙련된 사전 평가

일상적인 사육 절차를 개선하기 위해 실험실 토끼 훈련

일상적인 사육 절차를 개선하기 위해 실험실 토끼 훈련