This work was supported by The National Institute of Health (NIH-2RO1NS033661) and by the Alabama Agricultural Experiment Station (HATCH ALA021-1-09017).

참고 : 여기서의 모든 절차에 제출하여 승인을 IACUC (연구 준수 사무소)에 의해 NIH의 지침에 따라 실시 하였다되었다. 행동 테스트 패러다임에 사용 된 마우스는 순진하고 다른 시험에 사용되지 않았다. 이 프로토콜에 사용되는 C57BL / 6 야생형과 똑 마우스는 9 이전에 설명하고 여기에 제시된 데이터는 원고에서 있습니다. 테스트 룸과 오픈 필드 장치 1. 준비 <ol><li> 네 활동 챔버로 구성된 여러 단위 열기 필드 미로 (OFM)를 사용하는 것은 이러한 분석 (그림 1)에 사용되었다. 각 챔버 측정 50cm (길이) 50cm (폭) 38cm (높이) x 및 화이트 고밀도 및 비 - 다공성 플라스틱으로 제작 된 X. </li><li> 미로의 벽이 부드러운 동안 보행시 견인을위한 미로의 바닥 질감입니다. 미로 사분면이 시험의 목적을 위해 완전히 비어있다. 이 프로토 나머지 고려COL 상술 미로 단일 사분면 OFM을 설명하기 위해 이용 될 것이다. </li><li> 이전 주제 마우스로 남아있는 향기 단서를 제거하기 위해 사용하기 전에 95 %의 에탄올과 이후 테스트하기 전에 실을 닦습니다. </li><li> 에탄올은 쥐를 테스트에 전에 완전히 증발하도록 허용합니다. 이것은 각 테스트 세션 사이에 5 ~ 10 분 정도 걸릴 수 있습니다. </li><li> 이 분석을 위해, 기록 및 마우스 움직임을 평가 PanLab / 하버드 장치로부터 SMART 비디오 추적 소프트웨어를 사용한다. 주 : 모든 CM 영상 추적 카메라 및 소프트웨어는 오픈 필드 미로 결과를 시험 대상을 추적하고 평가할 수있다. 최종 사용자가 교정하는 방법을 이해하고 각 분석에 사용되는 소프트웨어를 실행하는 것은 매우 중요하다. 카메라와 소프트웨어가 제대로 제조업체의 지시에 따라 보정하는 경우에 상관없이 비디오 카메라 및 사용 추적 소프트웨어는 최상의 결과를 얻을 수있다. </li><li> 시험 I 수행NA 표준 미로 장치 및 소프트웨어를 실행하는 데 필요한 컴퓨터를 포함 할 수있는 공간을 조명. 천장에 부착 또는 카메라 렌즈가 미로 전체 영역 (도 2)을 참조 할 수있는 승강 지원 시스템을 이용하여 어느 미로 상기 비디오 카메라를 일시. </li><li> 시험 인간 관리자로서, 마우스의 행동에 영향을하지 않도록 미로에 피험자에 의해 완전히 관측 될 방에 공간이 충분해야. </li></ol> 2. 활동을 측정 할 수있는 소프트웨어를 준비 <ol><li> 비디오 추적 소프트웨어를 엽니 다. </li><li> 소프트웨어가 열린 후, &quot;데이터 수집&quot;탭이 옵션을 열려면 클릭 한 번 아래에있는 &quot;단일 주제 추적&quot;옵션에 커서를 이동합니다. </li><li> 화면 아래쪽에있는 &quot;정적 배경&quot;옵션을 선택합니다. </li><li> 선택 후 &quot;정적 배경&quot;를 선택이다N, 이는 앞서 피험자의 첨가로 미로의 이미지를 촬영하기 위해 소프트웨어를 사용하는 것이 필요하다. 이렇게하려면 스크린과 한 번의 클릭의 아래쪽에있는 &quot;사진&quot;버튼에 커서를 이동합니다. 주 : 소프트웨어 추적 처리 동안 촬영 화상으로부터 감산 될 것이다 시험 대상없이 시나리오의 사진을 찍을 것이다. 에만 피사체의 움직임이 소프트웨어에 의해 분석되는 경우가 빈번하게 발생한다. </li><li> 상기 촬영 배경 이미지가 완전히 화면 하단에있는 &quot;테스트&quot;버튼에 커서를 이동 한 번 클릭하여 추적 소프트웨어에 의해 제거되는 것을 확인한다. 배경 이미지가 완전히 추적 이미지에서 제거되면 백색 고체 필드는 도시한다. 조명 조건 변경하거나 미로 실수로 이동하는 경우, 당신은 두 개의 이미지가 완벽하게 일치하지 않는 나타내는이 분야에서 검은 &quot;그림자&quot;를 볼 수있을 것입니다. 이 상황을 해결하려면 인트를 반복P 2.4 이상. </li><li> 배경 설정을 확인한 후, 수집 시간 동안 제어되는 방식을 구성하는 타이밍 옵션을 사용. 이렇게하려면 &quot;구성&quot;탭으로 커서를 이동 한 후 &quot;타이밍&quot;제목을 클릭하면됩니다. 실험 매개 변수를 입력합니다 새로 열린 창을 사용합니다. </li><li> 이 프로토콜의 경우, 10 분 추적 기간으로 &quot;프로그램 된 시간&quot;옵션을 선택했다. 미로의 중앙에 위치시키고 마우스를 추적 개시전 멀어 사용자 시간을 허용하기 위해 5 초에 &quot;대기주기&quot;를 설정한다. 시험 기간 동안 10 분의 &quot;획득 시간&quot;을 입력한다. &quot;프로그램 시간 (10 분)이 끝나면&quot;자동 카메라와 소프트웨어의 추적 기능이 꺼집니다되는 설정 &quot;정지 제어&quot;를 설정합니다. </li><li> 모든 타이밍이 창을 닫습니다 설정 한 후 &quot;닫기&quot;버튼에 커서를 이동합니다. 이제 테스트를 시작할 준비가절차를 보내고. </li></ol> 열기 필드 테스트 3. 관리 주 :이 프로토콜에서 사용되는 소프트웨어 패키지는 한 번에 최대 16 개의 개별 마우스의 추적을 허용한다. 완성의 편의를 위해 위에서 언급 한 바와 같이, 여기에서 논의 된 프로토콜은 OFM의 하나의 사분면을 사용하여 하나의 마우스입니다. 이 프로토콜을 사용하고있는 기기의 경우, 4 개인 마우스의 최대 미로의 각 사분면을 사용하여 추적 할 수 있습니다. 멀티 인클로저 미로를 사용하는 경우, 그 정의 사분면의 첫 번째 주제 마우스를 배치 한 후, 분석을 추적하는 각각의 미로 사분면에 남아있는 마우스를 놓습니다. 이 프로토콜의 목적을 위해, 상기 명령은 미로의 사분면에 고유 한 것이다. <ol><li> 시험장에 자신의 주택 방에서 자신의 홈 케이지에 마우스를 가져. 쥐 실험을 시작하기 전에 30 분 이상 동안 절차 방에 적응하도록 허용. </li><li> 단일 m를 제거부드럽게 꼬리를 잡고 홈 케이지에서 여러개 동시에 마우스의 움직임을 추적 시작하기 위해 시작 버튼 하나 클릭하여 SMART 소프트웨어를 활성화하는 동안 열기 필드 미로의 중앙에 마우스를 놓습니다. 마우스가 미로의 주변 벽과 릴리스의 타이밍 즉시 이동하고 마우스 캡처를 추적하는 것은이 운동을 기록 일치해야하는 것은 정상입니다. </li><li> , 추적 소프트웨어는 움직임을 기록되는 시간 동안 하나의 10 분 기간 (그림 3)의 미로의 각 사분면에 걸쳐 주제 마우스의 무료 및 중단 운동을 허용합니다. </li><li> 시험 기간이 끝나면, 부드럽게 피사체 마우스 픽업 미로에서 제거하고 그의 홈 케이지로 복귀. </li><li> 미로를 청소하기 전에, 시각적으로 미로에 존재하는 배설물 boli 알약을 계산하고 수동으로 추가 분석을 위해 번호를 기록한다. </li><li> 모든 분변 알약을 제거하고 소변의 모든 관광 명소를 닦아. 바닥과 95 % 에탄올로 미로 사분면의 벽을 뿌려 깨끗한 종이 타월로 닦아냅니다. 허용 에탄올 용액 이전에 다른 마우스를 테스트에 완전히 건조. </li><li> 다음 마우스로 절차를 반복합니다. </li></ol> 4. 측정 및 시험 절차를 수행하는 동안 행동 분석 참고 : 측정을 위해, 오픈 필드 동작의 세 가지 측면 쉽게 (설명 참조)이 프로토콜을 사용하여 특징이다. 비디오 추적 소프트웨어에서 이러한 측정을 액세스하는 방법에 대한 간단한 명령어는 다음과 같다. <ol><li> SMART 소프트웨어의 주 화면에서, 존 편집기를 엽니 다 &quot;영역&quot;탭을 클릭 한 번으로 &quot;정의&quot;에 커서를 이동합니다. </li><li> SMART 소프트웨어 사용자 설명서의 자세한 설명은 추적 경로에 오버레이 영역 또는 그리드를 정의 하는가에 따라. 여기서, 소프트웨어는 미로의 바닥을 덮는 10cm 정사각형의 5 × 5 그리드 (정의하는 데 사용 된 <strong&gt; 그림 4). 앞서 존 편집기를 종료하기 위해 만든 영역 파일을 저장해야합니다. </li><li> SMART 소프트웨어의 메인 화면에서 &quot;분석&quot;탭으로 커서를 이동 한 데이터 분석 창을여십시오. </li><li> &quot;파일&quot;탭으로 커서를 이동하고 위에서 만든 영역 파일을 엽니 다. </li><li> &quot;구성&quot;탭으로 커서를 이동하고 &quot;트랙 분석&quot;옵션을 엽니 다. 이것은 &quot;단일 주제 분석 구성&quot;창이 열립니다. <ol><li> &quot;표준&quot;탭으로 커서를 이동시키고 포함 된 매개 변수 상자 (오른쪽)에 사용 가능한 매개 변수 상자 (왼쪽)에서 &quot;여행하고 거리&quot;매개 변수를 이동합니다. </li><li> &quot;영역 전환&quot;탭으로 커서를 이동하고 위의 포함 된 매개 변수 상자에 모든 적절한 매개 변수를 이동합니다. </li><li> &quot;전체 트랙&quot;상자가 창 하단에 선택되어 있는지 확인합니다. </li><li> 모OK 버튼에 커서를했습니다 및 단일 주제 분석 구성 창을 닫습니다. 참고 : 수행하고자하는 분석에 따라, 많은 다른 옵션은 분석에서 내 데이터에이 창에서 선택 될 수있다. 매개 변수 데이터의 분석을위한 가장 중요한 결정하기 위해 특정 프로그램의 자세한 사용 설명서를 읽어 보시기 바랍니다. </li></ol></li><li> 프로그램 창의 왼쪽 상단의 파일 탭에서 단일 주제 트랙 창을 열고 모든 트랙이 분석되고 옆에 체크 표시를합니다. 창 상단에있는 확인 표시 버튼에 커서를 이동하고 트랙 Explorer 창을 닫습니다. </li><li> 데이터 분석 창에서 &quot;이동&quot;버튼에 커서를 이동하고 하나의 트랙 데이터의 분석을 시작합니다. </li><li> 분석 데이터 중 하나를 ASCII 텍스트 파일로 출력 할 수 있습니다 또는 직접 엑셀 스프레드 시트로 내보낼 수 있습니다. 출력 다에 사용하는 소프트웨어 프로그램의 출력 도구를 사용하여자신의 사용에 따. 참고 : 총 이동 거리 및 표시 영역에서 보낸 시간은 위에 설명 된 데이터 분석 단계에 따라 출력됩니다. 다시, 단계 사용한 사용자 소프트웨어 등에 따라 다르고, 여기에 나타낸 이들 측정에 도달하도록 강조된다. 그러나 데이터 자체와 결과의 해석은 소프트웨어 프로그램의 유사한 독립적이어야한다. 그것은 그 테스트 관리자 바이어스 소프트웨어가 아닌 관리자에 의해 측정 된 데이터를 정량화 수집 된 모든 데이터와이 프로토콜에서 제거도 주목할 필요가있다. 따라서 기술 된 바와 같이 수집 된 데이터에 더 qualifiable 요소는 없다. </li></ol>

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W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+inactivation+of+p62+leads+to+accumulation+of+hyperphosphorylated+tau+and+neurodegeneration.">Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration.</a> J. Neurochem. 106, 107-120 (2008).</li><li>Simon, P., Dupuis, R., Costentin, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thigmotaxis+as+an+index+of+anxiety+in+mice:+influence+of+dopaminergic+transmissions.">Thigmotaxis as an index of anxiety in mice: influence of dopaminergic transmissions.</a> Behav. Brain Res. 61, 59-64 (1994).</li><li>Denenberg, V. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Open-field+behavior+in+the+rat:+what+does+it+mean.">Open-field behavior in the rat: what does it mean.</a> Ann. N.Y. Acad. Sci. 159, 852-859 (1969).</li><li>Stanford, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+open+field+test:+reinventing+the+wheel.">The open field test: reinventing the wheel.</a> J. Psychopharm. 21, 134-135 (2007).</li><li>Ennaceur, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tests+of+unconditional+anxiety+&#8211;+pitfalls+and+disappointments.">Tests of unconditional anxiety &#8211; pitfalls and disappointments.</a> J. Phys. Behav. 135, 55-71 (2014).</li><li>Borta, A., Schwarting, R. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibitory+avoidance,+pain+reactivity,+and+plus-maze+behavior+in+Wistar+rats+with+high+versus+low+rearing+activity.">Inhibitory avoidance, pain reactivity, and plus-maze behavior in Wistar rats with high versus low rearing activity.</a> J. Phys. Behav. 84, 387-396 (2005).</li><li>Costall, B., Jones, B. J., Kelly, M. E., Naylor, R. J., Tomkins, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exploration+of+mice+in+a+black+and+white+test+box:+validation+as+a+model+of+anxiety.">Exploration of mice in a black and white test box: validation as a model of anxiety.</a> Pharmacol. Biochem. Behav. 32, 777-785 (1989).</li><li>Bouwknecht, J. A., Paylor, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pitfalls+in+the+interpretation+of+genetic+and+pharmacological+effects+on+anxiety-like+behavior+in+rodents.">Pitfalls in the interpretation of genetic and pharmacological effects on anxiety-like behavior in rodents.</a> Behav. Pharm. 19, 385-402 (2008).</li><li>Webster, D. G., Baumgardner, D. J., Dewsbury, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Open+field+behavior+in+eight+taxa+of+muriod+rodents.">Open field behavior in eight taxa of muriod rodents.</a> Bull. Psychonom. Soc. 13, 90-92 (1979).</li><li>Wilson, R. C., Vacek, T., Lanier, D. L., Dewsbury, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Open+field+behavior+in+muroid+rodents.">Open field behavior in muroid rodents.</a> Behav. Biol. 17, 495-506 (1976).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+phenotyping+of+transgenic+and+knockout+mice:+experimental+designs+and+evaluation+of+general+health,+sensory+functions,+motor+abilities+and+specific+behavioral+tests.">Behavioral phenotyping of transgenic and knockout mice: experimental designs and evaluation of general health, sensory functions, motor abilities and specific behavioral tests.</a> Brain Res. 835, 18-26 (1999).</li><li>Simon, P., Dupuis, R., Costentin, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thigmotaxis+as+an+index+of+anxiety+in+mice.+influence+of+dopaminergic+transmissions.">Thigmotaxis as an index of anxiety in mice. influence of dopaminergic transmissions.</a> Behav. Brain Res. 61, 59-64 (1994).</li><li>Miller, B. H., Schultz, L. E., Gulati, A., Su, A. I., Pletcher, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phenotypic+characterization+of+a+genetically+diverse+panel+of+mice+for+behavioral+despair+and+anxiety.">Phenotypic characterization of a genetically diverse panel of mice for behavioral despair and anxiety.</a> PLoS One. 5, e14458 (2010).</li><li>Tannenbaum, B., Anisman, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+chronic+intermittent+challenges+in+stressor-susceptible+and+resilient+strains+of+mice.">Impact of chronic intermittent challenges in stressor-susceptible and resilient strains of mice.</a> Biol. Psych. 53, 292-303 (2003).</li><li>Lister, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ethologically-based+animal+models+of+anxiety+disorders.">Ethologically-based animal models of anxiety disorders.</a> Pharmacol. Ther. 46, 321-340 (1990).</li><li>Kulesskaya, N., Voikar, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+mouse+anxiety-like+behavior+in+the+light-dark+box+and+open-field+arena:+role+of+equipment+and+procedure.">Assessment of mouse anxiety-like behavior in the light-dark box and open-field arena: role of equipment and procedure.</a> Phys. Behav. 133, 30-38 (2014).</li><li>Han, H., Du, W., Zhou, B., Zhang, W., Xu, G., Niu, R., Sun, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+chronic+fluoride+exposure+on+object+recognition+memory+and+mRNA+expression+of+SNARE+complex+in+hippocampus+of+male+mice.">Effects of chronic fluoride exposure on object recognition memory and mRNA expression of SNARE complex in hippocampus of male mice.</a> Biol. Trace Elem. Res. 158, 58-64 (2014).</li><li>Barrow, P., Leconte, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+influence+of+body+weight+on+open+field+and+swimming+maze+performance+during+the+post-weaning+period+in+the+rat.">The influence of body weight on open field and swimming maze performance during the post-weaning period in the rat.</a> Lab. Animals. 30, 22-27 (1996).</li></ol>

The authors have nothing to disclose.

열기 필드 미로 동물 행동 연구에서 가장 널리 사용되는 플랫폼 중 하나입니다. 중요하고, 종래의 2,4- ethological 파라미터 번호를 수집하여 OFM의 수행 동안 분석 될 수있다. 이 자료는 연구자가 불안 관련 감정적 인 행동 8 전체 운동 활성에 이르기까지 행동을 측정 할 수 있습니다. 그러나, OFM의 사용에도 단점은 있습니다. 한가지 문제는 어떤 교란 시험 세션 동안 조작 될 수있는 정...

The Open Field Maze (OFM) was initially developed in 1934 as a test to measure emotionality in rodents1. It has attained the status of being one of the most widely used measures of behavior in animal psychology2. It provides an easy and fairly rapid assessment of well-defined behaviors requiring no training to the test subject and little to no specialized training for the human administering the test. These attributes have led to wide-spread use of the open field maze in research extended to other animal species such as calves, pigs, rabbits, primates, honeybees and lobsters3. Part of its popularity arises from the fact that the psychological and physiological concepts underlying the tests are generally straight-forward and well understood. For example, it has been postulated that evolutionary forces have selected for a common response in animals such that most species display anxiety-mediated fear or flight responses to specific stimuli. Rodents for example, show distinct aversions to large, brightly lit, open and unknown environments4. We can assume they have been phylogenetically conditioned to see these types of environments as dangerous. All of these features are incorporated in the open field maze and form the basis of its use in behavioral paradigm testing.
An open field maze consists of a wall-enclosed area that is of sufficient height to prevent the subject from escaping. Typical maze shapes are circular or square with an area large enough, based on the size of the subject tested, to elicit a feeling of openness in the center of the maze. A number of variables can be scored in the open field maze with most parameters involving differing types of motor activity2. Ambulation is the most common behavior studied but others such as latency or rearing can also be measured. Most often, rodent behavior is analyzed in a bare maze. However, the addition of objects, either one or many to the maze floor, adds the ability to see how the subject interacts with novel additional stimuli2. Relevant parameters when objects are presented are typically the number of approaches to an object or in some cases, preference or aversion for one object over another.
Many behavioral tests of anxiety are based on the subject animal&#8217;s body activity and locomotion5. Interpreting behavioral tests for emotionality while separating non-emotional confounding factors, such as motor activity, has been the subject of intense debate6,7. As the OFM was originally described, two measures of emotionality can be deduced, locomotor activity and fecal boli deposits or defecation1. However, these two measures have been shown in some studies to be unrelated supporting the conclusion that emotionality in rodents is multidimensional5. Regardless, discrepancies in the literature regarding these measures and emotionality or anxiety in mouse models may be attributed to differences in analysis criteria or differences in testing procedures. Studies have conclusively linked results from OFM analysis with other measures of anxiety when comparing mouse models8.

<table><tbody><tr><td>Multi Unit Open Field Test</td><td>San Diego Instruments, Inc.</td><td>White 7001-0354</td><td>Any single or multi unit open field maze can be used</td></tr><tr><td>SMART DT Tracking Software</td><td>PanLab/Harvard Apparatus</td><td>76-0695</td><td>Any tracking software can be utilized with this protocol</td></tr><tr><td>Sony 990x Video Camera Recorder</td><td>Sony</td><td>CCD-TRV328</td><td>Any suitable video camera can be attached to computer for recording tracking profiles.</td></tr></tbody></table>

use of the open field maze to measure locomotor and anxiety-like behavior in mice

Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of the most commonly used platforms to measure behaviors in animal models. It is a fast and relatively easy test that provides a variety of behavioral information ranging from general ambulatory ability to data regarding the emotionality of the subject animal. As it relates to rodent models, the procedure allows the study of different strains of mice or rats both laboratory bred and wild-captured. The technique also readily lends itself to the investigation of different pharmacological compounds for anxiolytic or anxiogenic effects. Here, a protocol for use of the open field maze to describe mouse behaviors is detailed and a simple analysis of general locomotor ability and anxiety-related emotional behaviors between two strains of C57BL/6 mice is performed. Briefly, using the described protocol we show Wild Type mice exhibited significantly less anxiety related behaviors than did age-matched Knock Out mice while both strains exhibited similar ambulatory ability.

대부분의 경우 실험군 당 균주 개인의 평균 개수는 충분한 관련성 통계를 생성하기 위해 약 20이다. 그러나이 숫자는 마우스 가용성에 따라 8-30의 범위 일 수있다. 필요한 측정 또는 비교에 따라, 또한 연령 유사한 피사체를 사용하는 것이 바람직하다. 열기 필드 미로에서 측정하는 제 틀림없이 가장 중요한 특정 매개 변수는 총 외래 거리입니다. 측정 단위는 비교를 위해 부?...

Watch this Scientific Journal Video about Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice at JoVE.com

Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice

A protocol is provided to use an Open Field Maze to access general locomotor activity, anxiety and emotionality in a laboratory mouse model.

열기 필드 미로의 사용은 마우스의 운동력과 불안 같은 행동을 측정하기 위해

Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of ...

use-open-field-maze-to-measure-locomotor-anxiety-like-behavior

Universidad San Sebastian

Research

JoVE Journal

Behavior

72.4K 조회수.  Auburn University. A protocol is provided to use an Open Field Maze to access general locomotor activity, anxiety and emotionality in a laboratory mouse model.

비디오: Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice

The Successive Alleys Test of Anxiety in Mice and Rats

The plus-maze was derived from the early work of Montgomery. He observed that rats tended to avoid the open arms of a maze, preferring the enclosed ones. Handley, Mithani and File et al. performed the first studies on the plus-maze design we use today, and in 1987 Lister published a design for use with mice. 
Time spent on, and entries into, the open arms are an index of anxiety; the lower these indices, the more anxious the mouse is. Alternatively, a mouse that spends most of its time in the closed arms is classed as anxious. 
One of the problems of the plus-maze is that, while time spent on, and entries into, the open arms is a fairly unambiguous measure of anxiety, time in the central area is more difficult to interpret, although time spent here has been classified as &#x201C;decision making&#x201D;. In many tests central area time is a considerable part of the total test time.
Shepherd et al. produced an ingenious design to eliminate the central area, which they called the &#x201C;zero maze&#x201D;. However, although used by several groups, it has never been as widely adopted as the plus-maze. 
In the present article I describe a modification of the plus-maze design that not only eliminates the central area but also incorporates elements from other anxiety tests, such as the light-dark box and emergence tests. It is a linear series of four alleys, each having increasing anxiogenic properties. It has given similar results to the plus-maze in general. Although it may not be more sensitive than the plus-maze (more data is needed before a firm conclusion can be reached on this point), it provides a useful confirmation of plus-maze results which would be useful when, for example, only a single example of a mutant mouse was available, as, for example, in ENU-based mutagenesis programs.

The plus-maze measures anxiety-like behaviour in rodents. There are two opposite closed and two opposite open arms; anxious rodents avoid the open arms. The central area is neither completely open nor closed, so time spent here is ambiguous and difficult to interpret. Here a modification of the plus-maze protocol eliminating this area is described.

마우스 및 쥐에있는 불안의 연속 골목길 테스트

The plus-maze was derived from the early work of Montgomery. He observed that rats tended to avoid the open arms of a maze, preferring the enclosed ones.  ...

연구

행동분석학

Low-stress Route Learning Using the Lashley III Maze in Mice

Many behavior tests designed to assess learning and memory in rodents, particularly mice, rely on visual cues, food and/or water deprivation, or other aversive stimuli to motivate task acquisition. As animals age, sensory modalities deteriorate. For example, many strains of mice develop hearing deficits or cataracts. Changes in the sensory systems required to guide mice during task acquisition present potential confounds in interpreting learning changes in aging animals. Moreover, the use of aversive stimuli to motivate animals to learn tasks is potentially confounding when comparing mice with differential sensitivities to stress. To minimize these types of confounding effects, we have implemented a modified version of the Lashley III maze. This maze relies on route learning, whereby mice learn to navigate a maze via repeated exposure under low stress conditions, e.g. dark phase, no food/water deprivation, until they navigate a path from the start location to a pseudo-home cage with 0 or 1 error(s) on two consecutive trials. We classify this as a low-stress behavior test because it does not rely on aversive stimuli to encourage exploration of the maze and learning of the task. The apparatus consists of a modular start box, a 4-arm maze body, and a goal box. At the end of the goal box is a pseudo-home cage that contains bedding similar to that found in the animal&#x2019;s home cage and is specific to each animal for the duration of maze testing. It has been demonstrated previously that this pseudo-home cage provides sufficient reward to motivate mice to learn to navigate the maze1. Here, we present the visualization of the Lashley III maze procedure in the context of evaluating age-related differences in learning and memory in mice along with a comparison of learning behavior in two different background strains of mice. We hope that other investigators interested in evaluating the effects of aging or stress vulnerability in mice will consider this maze an attractive alternative to behavioral tests that involve more stressful learning tasks and/or visual cues.

The Lashley III maze is a route-learning task that does not rely on aversive stimuli or visual cues. It is thus a highly attractive option for evaluating learning and memory, especially in aging mice or otherwise where stress is a consideration.

마우스에 레쉴리 III 메이즈를 사용하여 낮은 스트레스 루트 학습

Many behavior tests designed to assess learning and memory in rodents, particularly mice, rely on visual cues, food and/or water deprivation, or other ...

신경과학

Barnes Maze Testing Strategies with Small and Large Rodent Models

Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land (Barnes) mazes. Improved performance over sessions or trials is thought to reflect learning and memory of the escape cage/platform location. Considered less stressful than water mazes, the Barnes maze is a relatively simple design of a circular platform top with several holes equally spaced around the perimeter edge. All but one of the holes are false-bottomed or blind-ending, while one leads to an escape cage. Mildly aversive stimuli (e.g.&#160;bright overhead lights) provide motivation to locate the escape cage. Latency to locate the escape cage can be measured during the session; however, additional endpoints typically require video recording. From those video recordings, use of automated tracking software can generate a variety of endpoints that are similar to those produced in water mazes (e.g.&#160;distance traveled, velocity/speed, time spent in the correct quadrant, time spent moving/resting, and confirmation of latency). Type of search strategy (i.e.&#160;random, serial, or direct) can be categorized as well. Barnes maze construction and testing methodologies can differ for small rodents, such as mice, and large rodents, such as rats. For example, while extra-maze cues are effective for rats, smaller wild rodents may require intra-maze cues with a visual barrier around the maze. Appropriate stimuli must be identified which motivate the rodent to locate the escape cage. Both Barnes and water mazes can be time consuming as 4-7 test trials are typically required to detect improved learning and memory performance (e.g.&#160;shorter latencies or path lengths to locate the escape platform or cage) and/or differences between experimental groups. Even so, the Barnes maze is a widely employed behavioral assessment measuring spatial navigational abilities and their potential disruption by genetic, neurobehavioral manipulations, or drug/ toxicant exposure.

The dry-land Barnes maze is widely used to measure spatial navigation ability in response to mildly aversive stimuli. Over consecutive days, performance (e.g.&#160;latency to locate escape cage) of control subjects improves, indicative of normal learning and memory. Differences between rats and mice necessitate apparatus and methodology changes that are detailed here.

크고 작은 설치류 모델 바네스 미로 테스트 전략

Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land ...

Place and Response Learning in the Open-field Tower Maze

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for examining how rats learn to use a place- or response-learning to successfully navigate in an open-field arena. Additionally, this protocol describes how the OFTM differs from other behavioral maze paradigms that are commonly used to study spatial learning in rodents. The OFTM described in this article was adapted from the one previously described by Cole, Clipperton, and Walt (2007). Specifically, the OFTM was created to test spatial learning in rodents without the experimenter having to consider how &#8220;stress&#8221; might play a role as a confounding variable. Experiments have shown that stress-alone can significantly affect cognitive function1. The representative results section contains data from an experiment that used the OFTM to examine the effects of estradiol treatment on place- and response-learning in adult female Sprague Dawley rats2. Future studies will be designed to examine the role of the hippocampus and striatum in place- and response-learning in the OFTM.

The Open-field Tower Maze (OFTM) is a maze created to study the behavioral and neural mechanisms of spatial learning (e.g., place- or response-learning) in rats. This maze is especially useful for experimenters who want to use a non-stressful maze paradigm to investigate spatial learning in their research.

오픈 필드 타워 미로를 취하게하고 응답 학습

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for ...

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 ...

Elevated Plus Maze for Mice

Although the mouse genome is now completely sequenced, the functions of most of the genes expressed in the brain are not known. The influence of a given gene on a specific behavior can be determined by behavioral analysis of mutant mice. If a target gene is expressed in the brain, behavioral phenotype of the mutant mice could elucidate the genetic mechanism of normal behaviors. The elevated plus maze test is one of the most widely used tests for measuring anxiety-like behavior. The test is based on the natural aversion of mice for open and elevated areas, as well as on their natural spontaneous exploratory behavior in novel environments. The apparatus consists of open arms and closed arms, crossed in the middle perpendicularly to each other, and a center area. Mice are given access to all of the arms and are allowed to move freely between them. The number of entries into the open arms and the time spent in the open arms are used as indices of open space-induced anxiety in mice. Unfortunately, the procedural differences that exist between laboratories make it difficult to duplicate and compare results among laboratories. Here, we present a detailed movie demonstrating our protocol for the elevated plus maze test. In our laboratory, we have assessed more than 90 strains of mutant mice using the protocol shown in the movie. These data will be disclosed as a part of a public database that we are now constructing.
Visualization of the protocol will promote better understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used in different laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test. 


The elevated plus maze test is one of the most widely used tests for measuring anxiety-like behavior in mice. Here, we present a movie showing the detailed procedures for conducting the test.

마우스에 대한 고가 플러스 메이즈

Although the mouse genome is now completely sequenced, the functions of most of the genes expressed in the brain are not known. The influence of a given ...

생물학

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. ...

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.

모터 기술, 분위기, 그리고 쥐에 있는 인식의 반복 된 평가 행동 테스트 배터리

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and ...

Investigating Migraine-Like Behavior Using Light Aversion in Mice

Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be used as a behavioral surrogate for the migraine symptom of photophobia. To test for light aversion, we utilize the light/dark assay to measure the time mice freely choose to spend in either a light or dark environment. The assay has been refined by introducing two critical modifications: pre-exposures to the chamber prior to running the test procedure and adjustable chamber lighting, permitting the use of a range of light intensities from 55 lux to 27,000 lux. Because the choice to spend more time in the dark is also indicative of anxiety, we also utilize a light-independent anxiety test, the open field assay, to distinguish anxiety from light-aversive behavior. Here, we describe a modified test paradigm for the light/dark and open field assays. The application of these assays is described for intraperitoneal injection of calcitonin gene-related peptide (CGRP) in two mouse strains and for optogenetic brain stimulation studies.

Rodents are not able to report migraine symptoms. Here, we describe a manageable test paradigm (light/dark and open field assays) to measure light aversion, one of the most common and bothersome symptoms in patients with migraines.

마우스에서 가벼운 혐오감을 이용한 편두통과 같은 행동 조사

Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as ...

행동 테스트를 사용하여 Angelman Syndrome의 Murine 모델 검증

Behavioral Characterization of an Angelman Syndrome Mouse Model

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of AS. We use the rotarod learning paradigm, detailed gait analysis, and nest building test to detect and characterize animal motor impairments. We test animal emotionality in the open field and elevated plus maze tests, as well as the affect in the tail suspension test. When AS mice are tested in the open field test, the results should be interpreted with care, since motor dysfunctions influence mouse behavior in the maze and alter activity scores.
The reproducibility and effectiveness of the presented behavioral tests has already been validated in several independent Uba3a mouse lines with different knockout variants, establishing this set of tests as an excellent validation tool in AS research. Models with the relevant construct and face validity will warrant further investigations to elucidate the pathophysiology of the disease and grant the development of causal treatments.

저자 스포트라이트: Angelman Syndrome 쥐 모델을 검증하기 위한 고도로 재현 가능한 행동 테스트 배터리 

This manuscript presents a set of highly reproducible behavioral tests to validate an Angelman syndrome mouse model.

Angelman 증후군 마우스 모델의 행동 특성

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of ...