我们感谢他在帮助发展中国家图片TM程序行为分析中西一夫。这项研究得到了赠款援助的探索性研究（19653081），格兰特在科学研究援助（二）（21300121），资助科研创新领域的援助（综合脑科学网）教育部，科学，体育和文化的日本，从日本神经信息学中心（NIJC）赠款，并从波峰与日本科学技术振兴机构（JST）鸟的赠款。

1。仪器设置<ol><li>自动修改T-迷宫器具（奥哈拉公司，东京，日本）建造25厘米高的墙壁白色的塑胶跑道。滑动门（S1，S2，S3，A1，A2，P1，P2）（图1），可以自动打开向下的迷宫被分成6个区（A1，A2，S1和S2的P1，P2的）。干面积S2组成的T（13×24厘米）的T武器包括A1和A2区（11.5×20.5厘米）。 P1和P2领域包括从手臂的连接通道（A1或A2区）开始舱（面积一）。 </li><li>每个手臂配备颗粒机，自动提供蔗糖颗粒（20毫克，公式5啧啧，TestDiet，里士满，美国），作为奖励。颗粒摄入鼠标是由红外传感器和检测，由计算机自动记录。 </li><li>电荷耦合器件（CCD）摄像机安装上述仪器监测的鼠标＆＃x2019的行为，设备和鼠标的图像被捕获计算机。 </li><li> T-迷宫仪器放置在一个隔音的房间（170×210×200厘米，奥哈拉公司，东京，日本）AS可能。该仪器是荧光灯照明，在我们的实验室在100勒克斯。光的强度可能弱于这勒克斯的水平，但应在举行期间的所有实验的水平不变。 </li></ol> 2。动物准备<ol><li>房子大约两到四只老鼠在房间温度控制，每笼（23±2℃）与12小时的光/暗周期（上午7:00灯），据以指导和既定协议，由当地动物保健和使用委员会。 </li><li>转让全部进入房间隔音笼子里含有老鼠从住房里的第一次审判开始前至少30分钟。 </li><li>所有的实验，应始终在同一时间内（例如，上午9:00至下午6:00）。在测试过程中PE荒漠化问题，从每种基因型或实验条件的对象应​​被测试在抵消秩序，有可能是因为在一天的时间任务的性能上的潜在影响。 </li></ol> 3。食品的限制<ol><li>实验开始之前，免费获得标准颗粒议员和水的小鼠。 </li><li>从1周前预培训会议，权衡小鼠每天喂标准颗粒议员，以维护他们的自由喂养体重的80％至85％，整个实验。 </li><li>除了标准颗粒议员在他们的家笼八个每鼠标蔗糖颗粒提供每天习惯于直到开始前培训班蔗糖颗粒。 </li></ol> 4。习惯以仪器和预培训<ol><li>地方的地方九蔗糖颗粒每鼠标到每一个仪器的6个车厢，和存款的一种颗粒到每个托盘食品掌柜中心。 </li><li>放入仪器所有小鼠在笼子里，并允许他们自由探索的器具用30分钟打开所有的门。 </li><li>从1天的习惯后，老鼠每天都受到前培训。与所有的门关闭，沉淀在存放食品托盘，面积A1地方鼠标。如果鼠标消耗的颗粒或5分钟的推移，转让面积A2和鼠标再次开始前的培训。这样的训练是每天重复5次，并一直持续到小鼠的消耗超过80％的颗粒。 </li><li>完成前培训班后，老鼠受到强制交替工作或左，右的歧视任务。 </li></ol> 5。强制交替任务<ol><li>在被迫交替的任务，每个试验包括一个被迫的选择运行FOLlowed自由选择运行。 </li><li>任务开始运行应用程序（图片TM），并将其放置在开始框（区一）鼠标。 </li><li>点击“开始”按钮，并开始采用强制选择运行。在此运行，起始盒（门S2）和任区A1（A1门）或面积A2（门A2）的门被打开，蔗糖颗粒自动敞开大门，以该地区的食品托盘。鼠标被允许进入该地区，并消耗沉淀。当老鼠吃了沉淀，食品托盘的手臂，目前停留鼠标（无论是门P1或P2）附近的门被打开。然后，鼠标接近门（S1或S3），邻国开始框，门P1或P2关闭和打开门的S1（或S3），使鼠标可以返回到起始框中。如果鼠标不能吃的30秒内的颗粒，响应被记录为“不作为的错误”。然后，颗粒自动从食品托盘和T他手臂的门，小鼠逗留（无论是P1或P2）被打开，然后鼠标就可以返回到起始框中。 </li><li>强迫选择运行之后，自由选择运行自动开始。门S2，A1和A2两个门被打开。鼠标可以选择两者之间的武器。如果鼠标进入对面的手臂，它被迫选择在强迫选择运行，它的反应被认为是“正确的”和鼠标接收蔗糖沉淀。如果鼠标不能吃的30秒内的颗粒，响应被记录为“不作为的错误”，球是从食物托盘自动删除。如果鼠标进入参观强迫选择任务相同的手臂，鼠标被限制为10秒，作为惩罚（“错误”响应）的区域内。然后，打开门的P1（S1）和P2（或S3），鼠标就可以返回到起始框中。 </li><li>鼠标是连续10个试验，在每节天（截止时间为50分钟）。对照组小鼠每天训练组平均达到80％正确的响应在会话。正确的反应组平均计算各组会议由平均每个鼠标的正确反应。 </li><li>训练的标准，控制和/或实验小鼠后，可以进一步测试延迟交替任务的小鼠，通过插入3 - ，10 - ，30 - 或60-S之间的强迫选择和自由选择延迟运行。 </li><li>每次会议后，返回到他们的家庭笼的小鼠，和清洁超级次氯酸水（pH值6-7）的器具，以防止嗅觉线索为基础的偏见。 </li></ol> 6。左，右的歧视任务<ol><li>在左，右的歧视任务，每个鼠标自由选择运行了10年或20试验。蔗糖颗粒总是被交付的武器之一，即目标手臂食品托盘。小鼠学习进入目标手臂。目标位置手臂是不变的整个审判和会议，并通过控制实验小鼠抵消。 </li><li>任务开始运行的应用程序（图片TM），并放入启动框（区一）鼠标。 </li><li>点击“开始”按钮，并开始自由选择运行。在此运行，S2的门，A1和A2两个门被打开，颗粒机自动提供了一个球的目标臂的食品托盘。允许鼠标的左边和右边的武器之间自由选择。当鼠标进入目标的手臂，它被认为是一个正确的回应。如果老鼠吃的颗粒或30秒的推移，门P1（或P2）被打开。当鼠标接近穿过该地区的P1（或P2）开始框，打开门S1（或S3），使鼠标可以返回到起始框中。 </li><li>鼠标通常受到10至20日在每一天的会议（截止时间为50分钟）的连续试验。对照组小鼠每天训练组平均达到了80％CORR在一个会话等反应。正确的反应组平均计算各组会议由平均每个鼠标的正确反应。 </li><li>小鼠达到标准后，可以给予额外会议的老鼠，以评估保留内存和再学习，通过插入一个会话之间的几个星期的延迟，或放置在对面的奖励，以评估行为的灵活性，手臂先前unbaited（即逆转学习），作为必要的。 </li><li>每次会议后，返回到他们的家庭笼的小鼠，和清洁超级次氯酸水（pH值6-7）的器具，以防止嗅觉线索为基础的偏见。 </li></ol> 7。图像分析<ol><li>在T-迷宫装置的行为是由一台摄像机连接到计算机和图像存储在TIFF格式记录。用于采集和分析行为数据（图片TM）应用程序是基于对公共领域的图片J计划（开发韦恩在国家精神卫生研究所和Rasband可在<a hef="http://rsb.info.nih.gov/ij/">http://rsb.info.nih.gov/ij/</a> ），这是由宫川刚（可通过奥哈拉公司，日本东京）修改。 </li><li>图片TM程序自动生成文本文件正确反应的百分比，延迟时间（秒），完成会话，行驶距离，在会议期间和在会议遗漏的错误。此外，鼠标，原始的位置数据，以及原料在每次运行时的响应数据（正确，遗漏或错误）跟踪图像的生产和储存。 </li></ol> 8。统计分析每个行为数据分析由双向（实验条件（例如，基因型）X会话或实验条件X时滞）重复测量的方差分析。 9。代表结果马 - 例如由α-CaMKII的+ / T-迷宫表现乐小鼠和野生型控制窝（只C57BL/6J背景）（11-18周龄，10例被迫交替或左，右的歧视任务组）在图2-4所示。由于α-CaMKII的+ / -小鼠表现出高水平的侵略朝笼交配2,3，两个突变体和对照组小鼠单独安置在一个塑料笼断奶后（22.7 x 32.3 x 12.7厘米）。实验动物保健制度和藤田保健大学使用委员会批准。 在被迫交替任务，对照组将越来越多地了解做出正确的选择，通常可以达到约1至2周（图2A），平均80％的正确反应的标准。与对照组小鼠相比，α-CaMKII的+ / - 小鼠表现出的正确反应的比例显着降低（基因型：F（1,18）= 29.04，P &lt;0.0001）和较短的潜伏期（基因型：（1,18）= 8.88 ，P = 0.008;基因型X会话F（9,162）= 2.24，P = 0.0218），走过了短D.istance（基因型：F（1,18）= 8.67，P = 0.0086;基因型X会话F（9,162）= 3.19，P = 0.0014）比对照组（图2A，B和C）。没有显着影响的基因型被发现遗漏错误（图2D）。此外，在延迟交替任务正确的选择百分比的α-CaMKII的+ / - 小鼠均显着高于野生型小鼠在任何延迟时间（基因型：F（1,18）= 38.781，P &lt;0.0001;时滞：F（3,54）= 8.074，P = 0.0002;时滞基因型x：F（3,54）= 0.223，P = 0.88;图3）。这些结果表明，该突变体显示受损的表现比对照组小鼠突变小鼠虽然可以执行的任务比对照组快，表明α-CaMKII的缺乏导致工作记忆赤字。 在左，右的歧视任务，α-CaMKII的正确选择百分比+ / - 突变逐渐增加跨会话，类似的对照组（图4A）。此外，当1个月的延迟会话之间插入有％正确的突变和对照组之间没有显着性差异。在被迫交替任务，α-CaMKII的+ / - 突变表现出显着缩短延迟完成会话（基因型：F（1,18）= 12.12，P = 0.0027）和短距离行驶在会议期间在设备（基因型：F（1,18）= 25.08，P &lt;0.0001;基因型X会话：（15,270）= 2.83，P = 0.0004，高于整个培训班（图4B和C），对照组）。这些数据表明，缺乏α-CaMKII的剂量不会影响这个任务评估参考记忆。然而，在逆转学习会，α-CaMKII的+ / - 突变表现出的正确反应的比例显着降低（基因型：F（1,18）= 10.92，P = 0.0039;基因型X会话：F（5,90）= 5.54，P = 0.0002;图4A），并有更多的遗漏错误比对照组（基因型：F（1,18）= 17.12，P = 0.0006;图4D）。这些结果表明，α-CaMKII的+ / - 突变小鼠行为的灵活性降低。 &lt;一类p =的“jove_content”&gt; <img src="/files/ftp_upload/3300/3300fig1.jpg" alt="图1" /> 图1（A）T-迷宫被迫交替和左，右的歧视任务的仪器。数字引自隆夫等人 （2008）。 （二）以上的设备安装在CCD相机图像被抓获。 T-迷宫被分成6个区（A1，A2，S1和S2的P1，P2的）滑动门（S1，S2，S3，A1，A2，P1，P2）。 （三）在一个房间隔音设备和额外的迷宫线索的配置和方向。两个设备都放置在同一个方向朝面临在隔音室的墙壁，对象，如房间的门，在天花板上的日光灯，房间的墙壁，CCD相机的仪器，和机架容纳鼠标网箱设置。 <img src="/files/ftp_upload/3300/3300fig2.jpg" alt="图2" /> 图2。T-迷宫被迫交替任务。小鼠接受每天每sessio 10试验N。 （二）（一）正确反应率的数据，延迟时间（秒），（三）行驶距离（厘米）及（D）标准误差为每块两会代表的遗漏错误的数目，并分析双向重复测量方差分析。 α-CaMKII的+ / - 小鼠表现出正确的反应的比例较低（P &lt;0.0001）和较短的潜伏期（P = 0.008），行驶距离较短（P = 0.0086）比对照组小鼠在会话。 <img src="/files/ftp_upload/3300/3300fig3.jpg" alt="图3" /> 图3。T-迷宫被迫延误3，10，30，60秒交替任务。最后培训会议约24小时后，老鼠受到五个延迟会议。每延误正确反应的百分比表示标准错误的手段，双向重复测量方差分析进行分析。 α-CaMKII的+ / - 小鼠表现出任何延误，比对照组的正确反应的比例较低时间（P &lt;0.0001）。 <img src="/files/ftp_upload/3300/3300fig4.jpg" alt="图4" /> 图4。T-迷宫的左，右歧视任务。小鼠每天收到10或20个试验，在一个会话。 （一）正确反应率的数据，（二）延迟（秒），（三）行驶距离（厘米），（四）遗漏错误的数目代表作为标准误差为每块20个试验手段，双向重复测量方差分析进行了分析。在最初的培训课程和再学习会议的最后一次训练会议后1个月，正确反应的比例并没有显着不同α-CaMKII的+ / - 突变体和对照组之间。然而，突变小鼠，表明在逆转学习课程（P = 0.0039）比对照组的正确反应的比例显着降低。

<ol>
	<li>Takao, K., Toyama, K., Nakanishi, K., Hattori, S., Takamura, H., Takeda, M., Miyakawa, T., Hashimoto, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+long-term+memory+retention+and+working+memory+in+sdy+mutant+mice+with+a+deletion+in+Dtnbp1,+a+susceptibility+gene+for+schizophrenia.">Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia.</a> Mol. Brain. 1, 11-11 (2008).</li><li>Chen, C., Rainnie, D. G., Greene, R. W., Tonegawa, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abnormal+fear+response+and+aggressive+behavior+in+mutant+mice+deficient+for+alpha-calcium-calmodulin+kinase+II.">Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II.</a> Science. 266, 291-294 (1994).</li><li>Yamasaki, N., Maekawa, M., Kobayashi, K., Kajii, Y., Maeda, J., Soma, M., Takao, K., Tanda, K., Ohira, K., Toyama, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alpha-CaMKII+deficiency+causes+immature+dentate+gyrus,+a+novel+candidate+endophenotype+of+psychiatric+disorders.">Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders.</a> Mol. Brain. 1, 6-6 (2008).</li><li>Aultman, J. M., Moghaddam, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+contributions+of+glutamate+and+dopamine+receptors+to+temporal+aspects+of+rodent+working+memory+using+a+clinically+relevant+task.">Distinct contributions of glutamate and dopamine receptors to temporal aspects of rodent working memory using a clinically relevant task.</a> Psychopharmacology. 153, 353-364 (2001).</li><li>Papaleo, F., Yang, F., Garcia, S., Chen, J., Lu, B., Crawley, J. N., Weinberger, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dysbindin-1+modulates+prefrontal+cortical+activity+and+schizophrenia-like+behaviors+via+dopamine&#47;D2+pathways.">Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine&#47;D2 pathways.</a> Molecular Psychiatry. , 1-14 (2010).</li><li>Douglas, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cues+for+spontaneous+alternation.">Cues for spontaneous alternation.</a> J. Comp. Physiol. Psychol. 62, 171-183 (1966).</li><li>Dudchenko, P. A., Davidson, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rats+use+a+sense+of+direction+to+alternate+on+T-mazes+located+in+adjacent+rooms.">Rats use a sense of direction to alternate on T-mazes located in adjacent rooms.</a> Anim. Cogn. 5, 115-118 (2002).</li><li>Dudchenko, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+overview+of+the+tasks+used+to+test+working+memory+in+rodents.">An overview of the tasks used to test working memory in rodents.</a> Neurosci Biobehav. Rev. 28, 699-709 (2004).</li><li>Gerlai, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+continuous+alternation+task+in+T-maze+detects+hippocampal+dysfunction+in+mice:+A+strain+comparison+and+lesion+study.">A new continuous alternation task in T-maze detects hippocampal dysfunction in mice: A strain comparison and lesion study.</a> Behav. Brain. Res. 95, 91-101 (1998).</li><li>Wood, E. R., Dudchenko, P. A., Robitsek, R. J., Eichenbaum, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hippocampal+neurons+encode+information+about+different+types+of+memory+episodes+occurring+in+the+same+location.">Hippocampal neurons encode information about different types of memory episodes occurring in the same location.</a> Neuron. 27, 623-633 (2000).</li><li>Lee, I., Griffin, A. L., Zilli, E. A., Eichenbaum, H., Hasselmo, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gradual+translocation+of+spatial+correlates+of+neuronal+firing+in+the+hippocampus+toward+prospective+reward+locations.">Gradual translocation of spatial correlates of neuronal firing in the hippocampus toward prospective reward locations.</a> Neuron. 51, 639-650 (2006).</li><li>Crabbe, J. C., Wahlsten, D., Dudek, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetics+of+mouse+behavior:+interactions+with+laboratory+environment.">Genetics of mouse behavior: interactions with laboratory environment.</a> Science. 284, 1670-1672 (1999).</li><li>Wahlsten, D., Metten, P., Phillips, T. J., Boehm, S. L., Burkhart-Kasch, S., Dorow, J., Doerksen, S., Downing, C., Fogarty, J., Rodd-Henricks, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+data+from+different+labs:+lessons+from+studies+of+gene-environment+interaction.">Different data from different labs: lessons from studies of gene-environment interaction.</a> J. Neurobiol. 54, 283-311 (2003).</li><li>Matsuo, N., Yamasaki, N., Ohira, K., Takao, K., Toyama, K., Eguchi, M., Yamaguchi, S., Miyakawa, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+activity+changes+underlying+the+working+memory+deficit+in+alpha-CaMKII+heterozygous+knockout+mice.">Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice.</a> Front Behav. Neurosci. 3, 20-20 (2009).</li><li>Takao, K., Miyakawa, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Investigating+gene-to-behavior+pathways+in+psychiatric+disorders:+the+use+of+a+comprehensive+behavioral+test+battery+on+genetically+engineered+mice.">Investigating gene-to-behavior pathways in psychiatric disorders: the use of a comprehensive behavioral test battery on genetically engineered mice.</a> Ann. N. Y. Acad. Sci. 1086, 144-159 (2006).</li><li>Takao, K., Yamasaki, N., Miyakawa, T. <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+brain-behavior+phenotypying+of+genetically-engineered+mice+on+research+of+neuropsychiatric+disorders.">Impact of brain-behavior phenotypying of genetically-engineered mice on research of neuropsychiatric disorders.</a> Neurosci. Res. 58, 124-132 (2007).</li><li>Ikeda, M., Hikita, T., Taya, S., Uraguchi-Asaki, J., Toyo-oka, K., Wynshaw-Boris, A., Ujike, H., Inada, T., Takao, K., Miyakawa, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+YWHAE,+a+gene+encoding+14-3-3epsilon,+as+a+possible+susceptibility+gene+for+schizophrenia.">Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia.</a> Hum. Mol. Genet. 17, 3212-3222 (2008).</li><li>Nakatani, J., Tamada, K., Hatanaka, F., Ise, S., Ohta, H., Inoue, K., Tomonaga, S., Watanabe, Y., Chung, Y. J., Banerjee, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abnormal+behavior+in+a+chromosome-engineered+mouse+model+for+human+15q11-13+duplication+seen+in+autism.">Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism.</a> Cell. 137, 1235-1246 (2009).</li><li>Hashimoto-Gotoh, T., Iwabe, N., Tsujimura, A., Takao, K., Miyakawa, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=KF-1+Ubiquitin+Ligase:+An+Anxiety+Suppressor.">KF-1 Ubiquitin Ligase: An Anxiety Suppressor.</a> Front. Neurosci. 3, 15-24 (2009).</li><li>Ohno, M., Hiraoka, Y., Matsuoka, T., Tomimoto, H., Takao, K., Miyakawa, T., Oshima, N., Kiyonari, H., Kimura, T., Kita, T., Nishi, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nardilysin+regulates+axonal+maturation+and+myelination+in+the+central+and+peripheral+nervous+system.">Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system.</a> Nat. Neurosci. 12, 1506-1513 (2009).</li><li>Tanaka, H., Ma, J., Tanaka, K. F., Takao, K., Komada, M., Tanda, K., Suzuki, A., Ishibashi, T., Baba, H., Isa, T., Shigemoto, R., Ono, K., Miyakawa, T., Ikenaka, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mice+with+altered+myelin+proteolipid+protein+gene+expression+display+cognitive+deficits+accompanied+by+abnormal+neuron-glia+interactions+and+decreased+conduction+velocities.">Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuron-glia interactions and decreased conduction velocities.</a> J. Neurosci. 29, 8363-8371 (2009).</li><li>Sagata, N., Iwaki, A., Aramaki, T., Takao, K., Kura, S., Tsuzuki, T., Kawakami, R., Ito, I., Kitamura, T., Sugiyama, H., Miyakawa, T., Fukumaki, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comprehensive+behavioural+study+of+GluR4+knockout+mice:+implication+in+cognitive+function.">Comprehensive behavioural study of GluR4 knockout mice: implication in cognitive function.</a> Genes. Brain Behav. 9, 899-909 (2010).</li></ol>

没有利益冲突的声明。

被广泛用于评估工作和参考记忆，分别在啮齿类动物中的4,5，被迫交替和左，右歧视的任务，使用T-迷宫。在T-迷宫的任务，它是已知的，老鼠可以使用不同的策略来执行任务，对空间和非空间线索的基础，如迷宫外线索，配置房间的线索，迷宫的方向，等等， 6,7,8。在一个房间里，它的稳定性，缺乏或偏光房间线索存在的迷宫，方向和啮齿动物的能力，在房间里看到的线索可能会影响战略。因此，研究人员需要考虑的配置和定位仪器和线索，在房间中进行的实验和行为数据的解释。在我们的实验室，我们将在同一个方向朝墙在隔音室和集对象，如房间的门，在天花板上的日光灯，房间的墙壁，CCD相机，两个仪器面临仪器，机架，以适应老鼠笼，可作为额外的迷宫空间小鼠线索（图1C）。 在许多情况下，T-迷宫测试已手动进行人类实验者如下：在每个试验中，实验者把食物托盘上的蔗糖颗粒，并打开仪器开始测试了断头台门。然后，当鼠标进入的武器之一，实验者关闭的门，记录鼠标行为，从手臂传输鼠标的手开始框。可能的混杂变量的处理与鼠标基因型或实验条件下相互作用，可能影响T-迷宫的性能。即使在过去的十年中，已连续交替的任务，不涉及手动转移主体的目标手臂回到开始框中修改后的T-迷宫测试。9-11仪器，测试协议，许多环境变量大力相提并论，STAndardized行为测试并不总是产生类似的结果在不同的实验室12,13。每个实验室执行测试的具体实验者可能是唯一的，也可以影响小鼠的行为。此外，人类实验者是一般容易做出错误，如乱放蔗糖颗粒，打开或关闭其他门，以及为错误跟踪试验的数量和计时。为了减少混杂变量的影响和人为错误的发生，我们已制定并采用自动化的T-迷宫装置，通过视频与图像TM程序跟踪系统控制。改进后的T-迷宫仪器也有优势，让我们用微透析，电，光遗传学技术在T型迷宫的性能，因为门的设计进入地板。因此，自动化设备，是一个有用的工具，以方便工作和参考在啮齿类动物的记忆的神经生物学研究。 要启用自动和连续的一系列会议在审判执行，我们的协议有一些潜在的缺点。例如，在被迫交替任务，时间为小鼠回去到S1，从A1或A2可能会影响他们的表现。它可能不是一个严重的问题，虽然自住P1或P2区本身可以是一个空间的线索，在这两方面的长期或短期逗留在强迫选择运行，不得更改内存负载。另一个潜在的问题是老鼠的气味线索，而不是空间工作记忆，可以使用。然而，几个试验后，气味径可以覆盖多次，将成为难以被利用为线索。此外，在左歧视光任务，气味创新可能有助于找到一个跨连续试验的报酬的位置小鼠的嗅觉线索。线索可能影响整个试验的学习和记忆过程中的一个会话，这可能会是一个问题。然而，小鼠不能在一审中的一个会话使用气味跟踪策略，并因此第一次审判的表演将作为一个指标，是没有气味跟踪战略的一个潜在用途。 为代表的结果显示，控制C57BL/6J小鼠％的正确反应的逐渐增加，整个会议在这两个任务。调查结果证实，C57BL/6J小鼠学习，使正确的选择，在修改后的自动T-迷宫。在这项研究中，小鼠停留在80％左右的正确选择，没有更广泛的培训后（见图2A）。考虑到他们保持整个培训一些遗漏的错误，他们的动机可能是小鼠，以达到更高的性能水平如此之高。在被迫交替的任务，α-CaMKII的+ / - 小鼠表现出比对照组的正确反应的比例较低。因此，突变小鼠显示受损的表现相比，对照组小鼠在此TASK。这一结果是在八臂径向迷宫测试2,14获得以前的研究结果是一致的，提供进一步的证据，α-CaMKII的缺乏导致在工作记忆中的赤字，并被迫交替的任务自动化的T-迷宫仪器准确检测突变小鼠的记忆障碍。在左，右的歧视任务，结果表明，α-CaMKII的不足剂量不影响参考记忆。然而，在逆转学习会议的结果显示，α-CaMKII的不足可能会降低行为的灵活性。突变小鼠也显示比对照组更多的遗漏错误，逆转学习会议期间。遗漏错误的数目增加，可以减少学习的机会与奖励相关的手臂。因此，收购延迟的学习可能是由于遗漏错误的数目增加，在最初的会议，但不受损的逆转升收入。另一种可能性是，突变体，可以通过规则的变化，这可能会导致错误和遗漏干扰执行功能相混淆。因此，制订一个合理的结论，遗漏错误，应进行审查以及正确的选择比例。 TM程序生成的图像，前往额外的延迟时间和距离的结果以及完成会话的正确反应率和遗漏错误的数目。在潜伏期和距离的差异到完成会议可能被解释为在运动的活动水平，冲动倾向选择的武器，执行任务的动力，习惯性的任务，不同的学习策略水平等方面差异具有代表性的结果，α-CaMKII的+ / - 小鼠表现出较短的延迟和短距离比对照前往。事实上，αCaMKII的+ / - 小鼠相比呈hyperlocomotor活动到T他对照组3型可以依据指 ​​数的差异。 在我们的实验室，我们已经评估了超过36株遗传工程小鼠和野生型对照小鼠在T-迷宫测试使用的自动化设备，以阐明基因，大脑和行为15,16之间的关系。我们已经获得了超过1200只小鼠的原始数据大集，与已报道的几株在3,16-22突变小鼠的T-迷宫性能数据。株已经发表的研究文章中的数据都包含在“鼠标行为表型数据库”作为一个公共数据库（网址： <a href="http://www.mouse-phenotype.org/" target="_blank">http://www.mouse-phenotype.org/~~V</a> ）。一些研究表明，突变DTNBP1 1，NRD1 20 PLP1 21个基因小鼠显示工作记忆障碍。因此，我们的标准化协议与自动化的T-迷宫任务仪器是适合检测记忆功能的突变体和野生型对照小鼠之间的遗传效应。行为测试协议需要标准化，复制，跨实验室比较的结果。改进的T-迷宫设备的自动化测试程序，这将有助于整个实验室使用的协议的标准化。 在这部影片的文章显示，当前版本的设备和程序，可以让我们测试或黑色条纹的小鼠，但不是白化小鼠。现在，我们正在制作一个系统的修改后的版本，使白化小鼠进行测试。体内微透析，体内电，光遗传学实验，可以进行T-迷宫测试期间，由于门的设计走在地板下，该系统具有的优势。例如，一些研究人员可能试图探讨在海马神经元的电生理特性，在选择武器虽然可能需要从门和颗粒去除机制的驱动器，以尽量减少电噪声的设备有所改善。 两者合计，T-迷宫被迫交替和左，右歧视的任务，使用修改后的自动装置是有用的评估工作，并在小鼠参考记忆和行为的灵活性。

t-maze forced alternation and left-right discrimination tasks for assessing working and reference memory in mice

被迫交替使用T-迷宫的左，右的歧视任务已被广泛用于评估工作和参考记忆，分别在啮齿类动物中，。在我们的实验室中，我们评估的两种类型的内存，超过30株遗传工程小鼠，使用该设备的自动化版本。在这里，我们提出了修改后的T-迷宫视频跟踪系统和我们的协议在影片格式由计算机操作的仪器。 T-迷宫的设备，包括推拉门，可以自动打开向下，每个一开始框，一个T形的小巷，在一个盒子侧面两箱与自动颗粒掌柜，两个L形小巷分区关闭跑道。每一个L形的胡同是连接开始框，这样的小鼠可以返回到起始框，其中不包括对小鼠行为的影响实验者处理。该仪器还具有优势，在体内微透析，体内电，光遗传学技术部iques可以在T-迷宫的表现，因为门的设计进入地板。在这部影片中的文章中，我们描述了T-迷宫的任务，使用的自动化设备和T-迷宫的α-CaMKII的+ / - 小鼠，报告显示在八臂的径向迷宫任务，工作记忆障碍的性能。我们的数据表明，α-CaMKII的+ / - 小鼠显示工作记忆障碍，但没有参考记忆障碍，和以前的研究结果，使用八臂的径向迷宫任务，支持协议的有效性是一致的。此外，我们的数据表明，突变往往表现出逆转学习赤字，表明α-CaMKII的缺乏导致行为的灵活性降低。因此，T-迷宫测试，使用修改后的自动装置是有用的评估工作和小鼠参考记忆和行为的灵活性。

Watch this Scientific Journal Video about T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice at JoVE.com

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

本文介绍了T-迷宫测试，使用修改后的自动化设备，为评估小鼠学习和记忆功能的协议。

T-迷宫强迫交替和评估工作，并参考在小鼠记忆的左，右的歧视任务

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

t-maze-forced-alternation-left-right-discrimination-tasks-for

Research

JoVE Journal

Neuroscience

39.5K 次观看.  Fujita Health University. 本文介绍了T-迷宫测试，使用修改后的自动化设备，为评估小鼠学习和记忆功能的协议。

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

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.

评估挖洞，在小鼠的鸟巢建设和囤积

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

科研

神经科学

Morris Water Maze Test for Learning and Memory Deficits in Alzheimer&#39;s Disease Model Mice

The Morris Water Maze (MWM) was first established by neuroscientist Richard G. Morris in 1981 in order to test hippocampal-dependent learning, including acquisition of spatial memoryand long-term spatial memory 1. The MWM is a relatively simple procedure typically consisting of six day trials, the main advantage being the differentiation between the spatial (hidden-platform) and non-spatial (visible platform) conditions 2-4. In addition, the MWM testing environment reduces odor trail interference 5. This has led the task to be used extensively in the study of the neurobiology and neuropharmacology of spatial learning and memory. The MWM plays an important role in the validation of rodent models for neurocognitive disorders such as Alzheimer&#x2019;s Disease 6, 7. In this protocol we discussed the typical procedure of MWM for testing learning and memory and data analysis commonly used in Alzheimer&#x2019;s disease transgenic model mice.

Morris Water Maze Test for Learning and Memory Deficits in Alzheimer&#039;s Disease Model Mice

The Morris Water Maze is a behavioral task to test hippocampal-dependent learning and memory. It has been widely used in the study of neurobiology, neuropharmacology and neurocognitive disorders in rodent models.

在阿尔茨海默氏病模型小鼠学习和记忆障碍的Morris水迷宫测试

The Morris Water Maze (MWM) was first established by neuroscientist Richard G. Morris in 1981 in order to test hippocampal-dependent learning, including ...

Using Affordable LED Arrays for Photo-Stimulation of Neurons

Standard slice electrophysiology has allowed researchers to probe individual components of neural circuitry by recording electrical responses of single cells in response to electrical or pharmacological manipulations1,2. With the invention of methods to optically control genetically targeted neurons (optogenetics), researchers now have an unprecedented level of control over specific groups of neurons in the standard slice preparation. In particular, photosensitive channelrhodopsin-2 (ChR2) allows researchers to activate neurons with light3,4. By combining careful calibration of LED-based photostimulation of ChR2 with standard slice electrophysiology, we are able to probe with greater detail the role of adult-born interneurons in the olfactory bulb, the first central relay of the olfactory system. Using viral expression of ChR2-YFP specifically in adult-born neurons, we can selectively control young adult-born neurons in a milieu of older and mature neurons. Our optical control uses a simple and inexpensive LED system, and we show how this system can be calibrated to understand how much light is needed to evoke spiking activity in single neurons. Hence, brief flashes of blue light can remotely control the firing pattern of ChR2-transduced newborn cells.

Adult-born neurons expressing ChR2 can be manipulated in slice electrophysiological preparations in order to examine their contribution towards the function of olfactory neural circuits.

使用光刺激神经元的负担得起的LED阵列

Standard slice electrophysiology has allowed researchers to probe individual components of neural circuitry by recording electrical responses of single ...

Selective Viral Transduction of Adult-born Olfactory Neurons for Chronic in vivo Optogenetic Stimulation

Local interneurons are continuously regenerated in the olfactory bulb of adult rodents1-3. In this process, called adult neurogenesis, neural stem cells in the walls of the lateral ventricle give rise to neuroblasts that migrate for several millimeters along the rostral migratory stream (RMS) to reach and incorporate into the olfactory bulb. To study the different steps and the impact of adult-born neuron integration into preexisting olfactory circuits, it is necessary to selectively label and manipulate the activity of this specific population of neurons. The recent development of optogenetic technologies offers the opportunity to use light to precisely activate this specific cohort of neurons without affecting surrounding neurons4,5. Here, we present a series of procedures to virally express Channelrhodopsin2(ChR2)-YFP in a temporally restricted cohort of neuroblasts in the RMS before they reach the olfactory bulb and become adult-born neurons. In addition, we show how to implant and calibrate a miniature LED for chronic in vivo stimulation of ChR2-expressing neurons.

Selective Viral Transduction of Adult-born Olfactory Neurons for Chronic in vivo Optogenetic Stimulation

Adult-born neurons of the olfactory bulb can be optogenetically controlled using Channelrhodopsin2-expressing lentiviral injection in the rostral migratory stream and chronic photostimulation with an implanted miniature LED.

慢性成人出生的嗅觉神经元的选择性病毒转导在体内 Optogenetic刺激

Local interneurons are continuously regenerated in the olfactory bulb of adult rodents1-3. In this process, called adult neurogenesis, neural stem cells ...

The Mouse Forced Swim Test

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed.

The forced swim test is validated as an experimental approach to assess potential antidepressant efficacy in rodents. Experimental animals are placed in a tank of water and escape-related mobility behavior is quantified. The common procedures for the mouse version of this test are described.

小鼠强迫游泳实验

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental ...

Optical Recording of Suprathreshold Neural Activity with Single-cell and Single-spike Resolution

Signaling of information in the vertebrate central nervous system is often carried by populations of neurons rather than individual neurons. Also propagation of suprathreshold spiking activity involves populations of neurons. Empirical studies addressing cortical function directly thus require recordings from populations of neurons with high resolution. Here we describe an optical method and a deconvolution algorithm to record neural activity from up to 100 neurons with single-cell and single-spike resolution. This method relies on detection of the transient increases in intracellular somatic calcium concentration associated with suprathreshold electrical spikes (action potentials) in cortical neurons. High temporal resolution of the optical recordings is achieved by a fast random-access scanning technique using acousto-optical deflectors (AODs)1. Two-photon excitation of the calcium-sensitive dye results in high spatial resolution in opaque brain tissue2. Reconstruction of spikes from the fluorescence calcium recordings is achieved by a maximum-likelihood method. Simultaneous electrophysiological and optical recordings indicate that our method reliably detects spikes (&gt;97% spike detection efficiency), has a low rate of false positive spike detection (&lt; 0.003 spikes/sec), and a high temporal precision (about 3 msec) 3. This optical method of spike detection can be used to record neural activity in vitro and in anesthetized animals in vivo3,4.

Understanding the function of the vertebrate central nervous system requires recordings from many neurons because cortical function arises on the level of populations of neurons. Here we describe an optical method to record suprathreshold neural activity with single-cell and single-spike resolution, dithered random-access scanning. This method records somatic fluorescence calcium signals from up to 100 neurons with high temporal resolution. A maximum-likelihood algorithm deconvolves the underlying suprathreshold neural activity from the somatic fluorescence calcium signals. This method reliably detects spikes with high detection efficiency and a low rate of false positives and can be used to study neural populations in vitro and in vivo.

阈上的神经活动的单细胞和单穗的分辨率的光学的方法记录

Signaling of information in the vertebrate central nervous system is often carried by populations of neurons rather than individual neurons. Also ...

Vertical T-maze Choice Assay for Arthropod Response to Odorants

Given the economic importance of insects and arachnids as pests of agricultural crops, urban environments or as vectors of plant and human diseases, various technologies are being developed as control tools. A subset of these tools focuses on modifying the behavior of arthropods by attraction or repulsion. Therefore, arthropods are often the focus of behavioral investigations. Various tools have been developed to measure arthropod behavior, including wind tunnels, flight mills, servospheres, and various types of olfactometers. The purpose of these tools is to measure insect or arachnid response to visual or more often olfactory cues. The vertical T-maze oflactometer described here measures choices performed by insects in response to attractants or repellents. It is a high throughput assay device that takes advantage of the positive phototaxis (attraction to light) and negative geotaxis (tendency to walk or fly upward) exhibited by many arthropods. The olfactometer consists of a 30 cm glass tube that is divided in half with a Teflon strip forming a T-maze. Each half serves as an arm of the olfactometer enabling the test subjects to make a choice between two potential odor fields in assays involving attractants. In assays involving repellents, lack of normal response to known attractants can also be measured as a third variable.

A vertical, T-maze olfactometer is described for assaying the behavioral response of arthropods. The olfactometer allows the experimenter to measure choices performed by test subjects when subjected to two potential odor fields. Both attraction to and repulsion from odorants can be measured with this device.

的垂直T-迷宫的选择含量，节肢动物响应加味剂

Given the economic importance of insects and arachnids as pests of agricultural crops, urban environments or as vectors of plant and human diseases, ...

A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.

A novel low-cost human-machine interface for interactive post-stroke balance rehabilitation system is presented in this article. The system integrates off-the-shelf low-cost sensors towards volitionally driven electrotherapy paradigm. The proof-of-concept software interface is demonstrated on healthy volunteers.

人机界面集成的低成本传感器，具有神经肌肉电刺激系统中风后康复平衡

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing ...

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

Cold hypersensitivity is a serious clinical problem, affecting a broad subset of patients and causing significant decreases in quality of life. The cold plantar assay allows the objective and inexpensive assessment of cold sensitivity in mice, and can quantify both analgesia and hypersensitivity. Mice are acclimated on a glass plate, and a compressed dry ice pellet is held against the glass surface underneath the hindpaw. The latency to withdrawal from the cooling glass is used as a measure of cold sensitivity.
Cold sensation is also important for survival in regions with seasonal temperature shifts, and in order to maintain sensitivity animals must be able to adjust their thermal response thresholds to match the ambient temperature. The Cold Plantar Assay (CPA) also allows the study of adaptation to changes in ambient temperature by testing the cold sensitivity of mice at temperatures ranging from 30 &#176;C to 5 &#176;C. Mice are acclimated as described above, but the glass plate is cooled to the desired starting temperature using aluminum boxes (or aluminum foil packets) filled with hot water, wet ice, or dry ice. The temperature of the plate is measured at the center using a filament T-type thermocouple probe. Once the plate has reached the desired starting temperature, the animals are tested as described above.
This assay allows testing of mice at temperatures ranging from innocuous to noxious. The CPA yields unambiguous and consistent behavioral responses in uninjured mice and can be used to quantify both hypersensitivity and analgesia. This protocol describes how to use the CPA to measure cold hypersensitivity, analgesia, and adaptation in mice.

The Cold Plantar Assay (CPA) measures cold responsiveness between 30 &#176;C and 5 &#176;C, and can also measure cold adaptation. This protocol describes how to use the CPA to measure cold hypersensitivity, analgesia, and adaptation in mice.

测定冷灵敏度和适应小鼠一种简单廉价的方法

Cold hypersensitivity is a serious clinical problem, affecting a broad subset of patients and causing significant decreases in quality of life.  The cold ...

Assessing Spatial Learning and Memory in Small Squamate Reptiles

Clinical research has leveraged a variety of paradigms to assess cognitive decline, commonly targeting spatial learning and memory abilities. However, interest in the cognitive processes of nonmodel species, typically within an ecological context, has also become an emerging field of study. In particular, interest in the cognitive processes in reptiles is growing although experimental studies on reptilian cognition are sparse. The few reptilian studies that have experimentally tested for spatial learning and memory have used rodent paradigms modified for use in reptiles. However, ecologically important aspects of the physiology and behavior of this taxonomic group must be taken into account when testing for spatially based cognition. Here, we describe modifications of the dry land Barnes maze and associated testing protocol that can improve performance when probing for spatial learning and memory ability in small squamate reptiles. The described paradigm and procedures were successfully used with male side-blotched lizards (Uta stansburiana), demonstrating that spatial learning and memory can be assessed in this taxonomic group with an ecologically relevant apparatus and protocol.

This paper describes a modification of the Barnes maze, a standard rodent paradigm used to assess spatial memory and learning, for use in small squamate reptiles.

评估空间学习记忆小鳞类爬行动物

Clinical research has leveraged a variety of paradigms to assess cognitive decline, commonly targeting spatial learning and memory abilities. However, ...