Name: morris water maze test for learning and memory deficits in alzheimer's disease model mice
Uploaded: 2011-07-20T13:00:00.000+00:00
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Description: Watch this Scientific Journal Video about Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice at JoVE.com

Bu çalışma, Kanada Sağlık Araştırma Enstitüsü (CIHR) Townsend, Aile, ve Jack Brown ve Aile Alzheimer Araştırma Vakfı (WAS) tarafından desteklenmiştir. WS Kanada Araştırma Başkanı Alzheimer Hastalığı sahibi. PL NSERC Alexander Graham Bell Kanada Yüksek Lisans Bursu Doktora Sonrası Araştırma Ödülü ve Sağlık Araştırmaları Kıdemli Yüksek Lisans Bursu için Michael Smith Vakfı tarafından desteklenmiştir.

1. Hazırlık <ol><li> Ekipman hazırlık <ol><li> , 150cm çapında ve derinliği 50cm (Şekil 1) dairesel bir havuz alın. Eğer siyah fareler kullanarak, beyaz bir havuzu kullanılabilir; beyaz fareler kullanıyorsanız, siyah bir havuz kullanılmalıdır. </li><li> Test sırasında test edilen hayvan deneyi göremiyorum böyle oda düzenleyin. Bu perdeler ya da oda bölücüler ile yapılabilir. </li><li> Ve / veya bir yerde havuz su yüzeyinin üzerinde olacağını iç oda ile ilgili yüksek kontrast uzaysal işaretler yerleştirin. </li><li> Beyaz - beyaz bir havuzu, açık siyah bir havuzu için pleksiglas için havuzda bir 10cm çaplı bir platform yerleştirin. Havuz platform su yüzeyi üzerinde 1cm kadar su ile doldurun. Su, oda sıcaklığında (22 ° C) dengeye alalım. Su sıcaklığına bağlı olarak 1-3 gün sürebilir, ya da alternatif dengeleme hızlandırmak için sıcak su eklenebilir. </li></ol></li><li> Yazılım hazırlık <ol><li> Kamera piksel tabanlı bilgi, fiziksel mesafe bilgilerini oluşturmak, böylece bilgisayar yazılımı havuzu kalibre edin. 4 parçaya bölünür havuz bölün. Değişken bir bölge olarak her deneme ile değiştirebilirsiniz platform dilimi belirleyin. Her kadranda bir ve bir havuzun merkezi - 5 platformu subzones oluşturun. Kalibrasyon kaydedin ve kalan test gün boyunca kullanabilirsiniz. (Örneğin Şekil 2). </li><li> Maksimum 60 saniye kadar kısa bir deneme süresi ayarlayın. Fare, bu sefer daha önce platform bulursa, yazılım platformu bulundu yargılamayı durdurmak için program. </li><li> Otomatik izleme başlamak için program, deneyci çıkar test alanına belirtin. Yazılım paketi sağlayan herhangi bir &quot;yansıma minimizasyonu&quot; seçenekleri yararlanın. </li><li> Her kadranda harcanan yol uzunluğu, kaçış gecikme, ve zaman izleyin. </li></ol></li></ol> 2. 1. Gün: Görünür Platformu <ol><li> Bilgisayar programı <ol><li> Izleme yazılımı içine havuz kalibrasyon yükleyin. </li><li> Denemeniz için uygun bir yargılama arası aralığı ile, 5 çalışmalarda oluşturun. Platform konumu ve yönünü her deneme ile farklı başlangıç ​​Programı. Örneğin bir protokol için Tablo 1&#39;e bakınız. </li></ol></li><li> Prosedürü Test <ol><li> Fareler, konut tesis davranış odasına aktarın. Fareler havuz veya uzaysal işaretlerin göremez bir alanda tutun. Onları test etmeden önce en az 30 dakika için yeni ortama uyum olsun. </li><li> Görünürlüğünü artırmak için platform üzerinde bir bayrak yerleştirin. </li><li> Teste başlamak için, kuyruk tabanı ile ev kafes fare kaldırın. Test alanına getirmek olarak fare desteği. Kuyruk baz fare Kaldırma, yavaşça havuzun kenarına bakan, suyun içine fare yerleştirin. Test alanına hızla bırakın. </li><li> Fare 60 sn önce platform bulursa sonra cut-off, fare, 5 saniye süreyle platform üzerinde kalmak için izin ev kafesine geri. Fare platformu bulamazsa, platform üzerinde fare yeri ve ev kafes dönmeden önce 20 saniye boyunca orada kalmak için izin. </li><li> Iz tüm fareler için tekrarlayın. Yazılım programlanmış gibi, farklı bir platformda yer ve başlangıç ​​yönü ile sonraki her deneme başlayın. </li><li> Test tamamlandığında, fareler, konut tesis dönün. Fare kurutulur ve normotermi hayvan tesis dönmeden önce güvence altına alınmıştır. </li><li> Ertesi gün için hazırlık, platform bayrağı kaldırmak ve yüzey altında 1cm batığın platform havuzuna su eklemeyiniz. </li></ol></li></ol> 3. Gün 2-5: Gizli Platform <ol><li> Bilgisayar programı <ol><li> Izleme yazılımı içine havuz kalibrasyon yükleyin. </li><li> Denemeniz için uygun bir yargılama arası aralığı ile, 5 çalışmalarda oluşturun. Programı platform tüm denemeler ve gün boyunca aynı pozisyonda kalmak için yer, ama başlangıç ​​yön var, her gün, her deneme ile farklı. </li></ol></li><li> Prosedürü Test <ol><li> Siyah fareler için toksik olmayan, beyaz, toz, sıcaklık boya, havuz ekleyin ve iyice karıştırın. Yeterli su yüzeyinden batık platform görünmez olduğunu, boya kullanın. Beyaz fareler için, temiz su ve net bir pleksiglas platformu ile siyah bir havuz kullanılmalıdır. </li><li> 2.2.3 ve 2.2.6 için gerekli adımları izleyin. </li></ol></li></ol> 4. 6. Gün: Probe Deneme <ol><li> Bilgisayar programı <ol><li> Izleme yazılımı içine havuz kalibrasyon yükleyin. </li><li> Hiçbir platform bölge ile 1 deneme, ve bir başlangıç ​​yönde oluşturun. Gün 2-5 kullanılan platform kadranda en uzak başlangıç ​​yönü tercih edilir. Iz uzunluğu 60 saniyeye ayarlayın. </li></ol></li><li> Prosedürü Test <ol><li> Havuz platformu çıkarın. </li><li> 2.2.3 ve 2.2.6 için gerekli adımları izleyin. </li></ol></li></ol> 5. Veri analizi <ol><li> Ve her fare, ortalama her gün için 5 çalışmalarda, her bir test konusu için tek bir yol uzunluğu ve kaçış gecikme vermek için. Uygun şekilde kombine hata hesaplayın. Sadece 6 gün için, her bir fare için platform kadranda harcanan yol uzunluğu, kaçış gecikme ve zaman toplamak. </li><li> Gün 1 gruplar arasında herhangi bir farklılık varsa, büyük olasılıkla, öğrenme ve hafıza daha ziyade vizyon ile ilgili bir sorun. Sadece hiçbir farkları 1 gün görülürse analizi ile devam edin. </li><li> Veri seti için uygun istatistikleri kullanılarak günlük 2-5 öğrenme eğrileri karşılaştırın. A dik eğrisinin hızlı görev kazanıldığını gösteren, sığ bir eğri görev edinimi açığı temsil eder. 2 gün 5 gün elde edilen veriler ANOWA kullanılarak analiz edilmektedir. </li><li> 6 gün için, veri seti için uygun istatistikleri kullanılarak, önceden öğrenilen platformu kadranda harcanan zamanın yüzde karşılaştırın. Platform kadranda harcanan zaman daha yüksek bir yüzdesi daha yüksek bir bellek tutma seviyesi olarak yorumlanır. </li></ol> 6. Temsilcisi Sonuçlar Morris Su Labirent testi AD patogenezinde (7) ve valproik asit (VPA), transgenik AD modeli fareler AD tedavisi (6) &#39;nin ilaç potansiyeli hipoksi etkisi incelemek için kullanmışlardır. Şekil 3 VPA APP23 AD fare modeli (6) bellek açıkları etkisi bizim çalışmamızda raporlanan temsili bir sonucudur. 1. gün (görünür platformu çalışma), VPA tedavi ve kontrol grupları gecikme (Şekil 3A) ve her iki grup benzer motor ve görsel yetenekleri olduğunu gösteren yol uzunluğu (Şekil 3A) arasında hiçbir fark yoktur. Bu biz farelerin bayraklı platform ve çevresindeki çevre ipuçlarını görmek mümkün ve kabul edilebilir yüzebilirsiniz varsayalım. Gün 2-5 (gizli platform çalışmaların Gün 1 - 4) Örneğin, VPA tedavi edilen farelerde anlamlı olarak kontrollerden daha iyi bir performans gösterdiklerini öne kaçış gecikme (Şekil 3C) ve gruplar arasındaki yol uzunluğu (Şekil 3B) bir farklılık gösterir zamanla. Prob izi, farelerin daha önce gizli bir platform yerleştirildi üçüncü kadranda, içine yolculuk kaç kez, VPA tedavisi ile kontrol (Şekil 3E) göre anlamlı olarak daha fazla olduğunu son gün (Gün 6) gösteri. Bu veriler, VPA tedavisi APP23 farelerde görülen hafıza açıkları önemli ölçüde iyileştirdiğini göstermektedir. <img src="/files/ftp_upload/2920/2920fig1.jpg" alt="Şekil 1"/> Şekil 1. Morris Su Labirent görünür platformu test günü için donatım kurulum havuzu oda bölücüler kullanılarak deneyci korumalıdır. Mekansal ipuçları duvarları üzerinde bulunan ve istenirse, belki su yüzeyi üzerinde, havuzun iç yerleştirilir. Havuz yüzeyinden 1cm bulunan platform, temiz su ile doldurulur. Bir bayrak görünürlüğünü geliştirmek için bir platform üzerine yerleştirilmiştir. <img src="/files/ftp_upload/2920/2920fig2.jpg" alt="Şekil 2"/> Şekil 2. Havuz kalibrasyon gösteren herhangi bir-Labirent ™ Video İzleme Sistemi Ekran yakalama havuzu RTV24 Sayısallaştırıcı siyah ve beyaz analog izleme kamera tarafından yukarıdan bakıldığında. Bazı bölgeler yazılım içinde tanımlanmış ve toplam havuzu, 4 kadran ayrılmıştır. KB, KD, GB, GD, veya Merkez: beşinci, platformu bölgesi, beş olası yerleri ile denemeler arasında farklılık gösterebilir girilir. Bir kalibrasyon hattı (merkezi üzerinden işaretlendiyse hat) yazılım fiziksel mesafeleri piksel mesafeler dönüştürmek için izin eklenir. <img src="/files/ftp_upload/2920/2920fig3.jpg" alt="Şekil 3"/> Şekil 3. Morris Su Labirent Temsilcisi sonuçlar insan İsveççe mutant APP geni taşıyan 7 ay APP23 transgenik fareler, günlük VPA (n = 30 fare) veya araç çözüm (n = 30 fare) enjeksiyonları bir ay sonra (A) sırasında test edildi . görünür platform testlerin ilk gününde, VPA tedavi ve kontrol APP23 fareler görünür platformu üzerine kaçmak için benzer bir gecikme sergiledi. P&gt; 0.05 öğrencinin t-testi ile (B) VPA ile tedavi edilen ve görünür bir platform testi görünür platformu üzerine kaçan kontrolü APP23 fareler daha önce de benzer yüzme mesafeler vardı . P&gt; 0.05 ile öğrenci t-testi. (C) gizli bir platform testleri VPA APP23 fareler 3 üncü ve 4. gün, P gizli bir platform üzerine ANOVA ile &lt;0.001 kaçmak için bir kısa bir gecikme gösterdi tedavi. (D) VPA ile tedavi edilen APP23 fareler ANOVA ile gizli bir platform üzerine 3. ve 4. gün, P &lt;0.01 kaçan önce yüzme boyunun kısa bir (E) 6. gününde prob çalışmada, VPA ile tedavi edilen APP23 fareler gitti gizli bir platform daha önce yerleştirilmiş olan üçüncü kadranda, kontrollere göre önemli ölçüde daha fazla kez. * P &lt;0.005 öğrencinin t-testi. (J Exp Med DOI yayınlanan Deneysel Tıp 205, 2781-2789, 2008, Rockefeller Üniversitesi Basın, The Journal of Uyarlama ve yeniden basıldı... 10.1084/jem.20081588) (6). <table border="1"><tbody><tr><td>&nbsp;</td><td colspan="2"> 1. Gün </td><td> 2. Gün </td><td> 3. Gün </td><td> 4. Gün </td><td> 5. Gün </td><td> 6. Gün </td></tr><tr><td></td><td> Platform konumu </td><td> Başlangıç ​​Yönü </td><td colspan="4"> Platform Yer: GB Yer başlayarak aşağıdaki gibi: </td><td> Hiçbir platformu. </td></tr><tr><td> Deneme 1 </td><td> GB </td><td> S </td><td> W </td><td> N </td><td> N </td><td> E </td><td> N </td></tr><tr><td> Deneme 2 </td><td> KB </td><td> N </td><td> S </td><td> W </td><td> E </td><td> S </td><td></td></tr><tr><td> Deneme 3 </td><td> KD </td><td> S </td><td> N </td><td> E </td><td> W </td><td> W </td><td></td></tr><tr><td> Deneme 4 </td><td> Merkez </td><td> E </td><td> E </td><td> W </td><td> S </td><td> E </td><td></td></tr><tr><td> Deneme 5 </td><td> GD </td><td> W </td><td> S </td><td> S </td><td> N </td><td> N </td><td></td></tr></tbody></table> Tablo 1. Örnek su labirenti protokolü * * Not başlayan yönünü değiştirir ise platform konumu ve 1 günde yönünü değiştirmek başlayan, her iki gün 2-5 platform konumu sabit kalır, oysa ne kadar. 6 gün, herhangi bir platform ve tek bir dava yoktur. Farelerin daha önce öğrenilen platformu kadranda girmeden önce bazı mesafe seyahat gerekir, böylece 6 gün başlangıç ​​yönü önceki platform konumu (SW) uzak.

<ol>
	<li>Morris, R. G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+localization+does+not+require+the+presence+of+local+cues.">Spatial localization does not require the presence of local cues.</a> Learning and Motivation. 12, 239-260 (1981).</li><li>O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+the+hippocampal+place+cells.">A review of the hippocampal place cells.</a> Prog Neurobiol. 13, 419-439 (1979).</li><li>Scoville, W. B., Milner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Loss+of+recent+memory+after+bilateral+hippocampal+lesions.">Loss of recent memory after bilateral hippocampal lesions.</a> J Neurol Neurosurg Psychiatry. 20, 11-21 (1957).</li><li>Eichenbaum, H., Stewart, C., Morris, 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=Hippocampal+representation+in+place+learning.">Hippocampal representation in place learning.</a> J Neurosci. 10, 3531-3542 (1990).</li><li>Block, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+ischemia+and+behavioural+deficits.">Global ischemia and behavioural deficits.</a> Progress in Neurobiology. 58, 279-295 (1999).</li><li>Qing, H., He, G., Ly, P. T., Fox, C. J., Staufenbiel, M., Cai, F., Zhang, Z., Wei, S., Sun, X., Chen, C. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Valproic+acid+inhibits+Abeta+production,+neuritic+plaque+formation,+and+behavioral+deficits+in+Alzheimer's+disease+mouse+models.">Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models.</a> J Exp Med. 205, 2781-2789 (2008).</li><li>Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L. E., Song, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypoxia+facilitates+Alzheimer's+disease+pathogenesis+by+up-regulating+BACE1+gene+expression.">Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression.</a> Proc Natl Acad Sci U S A. , 18727-18732 (2006).</li><li>D'Hooge, R., De Deyn, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+the+Morris+water+maze+in+the+study+of+learning+and+memory.">Applications of the Morris water maze in the study of learning and memory.</a> Brain Research Reviews. 36, 60-90 (2001).</li><li>Brandeis, R., Brandys, Y., Yehuda, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+the+Morris+Water+Maze+in+the+study+of+memory+and+learning.">The use of the Morris Water Maze in the study of memory and learning.</a> Int J Neurosci. 48, 29-69 (1989).</li><li>Lipp, H. P., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetically+modified+mice+and+cognition.">Genetically modified mice and cognition.</a> Curr Opin Neurobiol. 8, 272-280 (1998).</li><li>Sandi, 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+role+and+mechanisms+of+action+of+glucocorticoid+involvement+in+memory+storage.">The role and mechanisms of action of glucocorticoid involvement in memory storage.</a> Neural Plast. 6, 41-52 (1998).</li></ol>

Tüm deneyler, British Columbia Hayvan Bakım ve Kullanım komitesi ve CIHR kurallar Üniversitesi ile uygun olarak yapılmıştır.

Yaş, cinsiyet, tür ve şekil değiştirme farklılıkları MWM performansı (8) etkiler. Çalışmalar erkek kemirgenler dişilere oranla daha iyi performans yaşlı farelerde, MWM kötü performansa sahip olduğunu göstermektedir, ayrıca yüzen sıçan (9, 10) daha farelerde daha belirgindir. Bu nedenle, bu unsurların tüm testler arasında eşit olmalıdır. Kanıtlar da vurguladı hayvanlar MWM (11) daha düşük performans göstermektedir, bu nedenle çevresel faktörler, sıcaklık, ışık, ve gürültü gibi stres, neden olabilir, izlenmeli ve görevi boyunca sabit tutulur olmalıdır.

<table border="1"><tbody><tr><th> Reaktifin Adı </th><th> Şirket </th><th> Yorumlar (isteğe bağlı) </th></tr><tr><td> AnyMaze video Takip Sistemi </td><td> Stoelting Şirket </td><td></td></tr><tr><td> Sıcaklık Boya </td><td> Reeves ve Poole Gruplar </td><td> Beyaz, toz </td></tr></tbody></table>

morris water maze test for learning and memory deficits in alzheimer&#39;s disease model mice

Morris Su Labirent (MWM) ilk sinirbilimci Richard G. Morris hipokampal-bağımlı öğrenme, mekansal memoryand uzun vadeli uzaysal 1 satın alınması da dahil olmak üzere test etmek amacıyla 1981 yılında kurulmuştur. MWM genellikle altı gün denemeler, mekansal (gizli platform) arasındaki fark olan ana avantajı ve konumsal olmayan (görünür platformu) koşullarına 2-4 oluşan nispeten basit bir işlemdir. Buna ek olarak, MWM test ortamı koku izi girişim 5 azaltır. Bu görev, uzamsal öğrenme ve hafıza nörobiyoloji ve Neuropharmacology çalışma yaygın olarak kullanılan yol açmıştır. MWM kemirgen modelleri doğrulama Alzheimer Hastalığı 6, 7 gibi bilişsel bozukluklar için önemli bir rol oynar. Bu protokolde, Alzheimer hastalığının transgenik modeli farelerde yaygın olarak kullanılan test öğrenme ve bellek ve veri analizi için MWM tipik bir prosedür tartışıldı.

Watch this Scientific Journal Video about Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice at JoVE.com

Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice

Morris Su Labirent hipokampal-bağımlı öğrenme ve hafıza test etmek için bir davranış iştir. Bu çalışmada, nörobiyoloji, Neuropharmacology ve bilişsel bozukluklar kemirgen modellerinde yaygın olarak kullanılır olmuştur.

Alzheimer Hastalığı Model Fareler Öğrenme ve Hafıza Açıkları Morris Su Labirent Testi

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

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Research

JoVE Journal

Neuroscience

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

127.1K Görüntüleme.  University of British Columbia. Morris Su Labirent hipokampal-bağımlı öğrenme ve hafıza test etmek için bir davranış iştir. Bu çalışmada, nörobiyoloji, Neuropharmacology ve bilişsel bozukluklar kemirgen modellerinde yaygın olarak kullanılır olmuştur.

Video: Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice

Shallow Water (Paddling) Variants of Water Maze Tests in Mice

When Richard Morris devised his water maze in 19817, most behavioral work was done in rats. However, the greater understanding of mouse genetics led to the mouse becoming increasingly important. But researchers found that some strains of mutant mice were prone to problems like passively floating or diving when they were tested in the Morris water maze11. This was unsurprising considering their natural habitat; rats swim naturally (classically, the "sewer rat"), whereas mice evolved in the dry areas of central Asia.
To overcome these problems, it was considered whether shallow water would be a sufficient stimulus to provide escape motivation for mice. This would also avoid the problems of drying the small creatures with a towel and then putting them in a heated recovery chamber to avoid hypothermia, which is a much more serious problem than with rats; the large ratio of surface area to volume of a mouse makes it particularly vulnerable to rapid heat loss.
Another consideration was whether a more natural escape strategy could be used, to facilitate learning. Since animals that fall into water and swim away from the safety of the shore are unlikely to pass on their genes, animals have evolved a natural tendency to swim to the edge of a body of water. The Morris water maze, however, requires them to swim to a hidden platform towards the center of the maze - exactly opposite to their evolved behavior. Therefore the paddling maze should incorporate escape to the edge of the apparatus. This feature, coupled with the use of relatively non-aversive shallow water, embodies the "Refinement" aspect of the "3 Rs" of Russell and Burch8.
Various types of maze design were tried; the common feature was that the water was always shallow (2 cm deep) and escape was via a tube piercing the transparent wall of the apparatus. Other tubes ("false exits") were also placed around the walls but these were blocked off. From the inside of the maze all false exits and the single true exit looked the same. Currently a dodecagonal (12-sided) maze is in use in Oxford, with 12 true/false exits set in the corners. In a recent development a transparent paddling Y-maze has been tested successfully.

Shallow Water Paddling Variants of Water Maze Tests in Mice

Mice can swim, but many strains appear to find this activity stressful. To overcome this problem mazes have been devised where escape from shallow water is used to motivate behaviour. These have been demonstrated to support learning at least as good as the traditional and widely used Morris water maze.

Farelerde Su Maze Testleri Sığ Su (kürek çekmeye) Türevleri

When Richard Morris devised his water maze in 19817, most behavioral work was done in rats. However, the greater understanding of mouse genetics led to ...

Davranış

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.

Farelerde Lashley III Labirent Düşük stres Rota Öğrenme

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

Nörobilim

Quantifying Cognitive Decrements Caused by Cranial Radiotherapy

With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For many patients afflicted with CNS and non-CNS malignancies, radiotherapy and chemotherapy offer the best options for disease control. These treatments however come at a cost, and nearly all cancer survivors (~11 million in the US alone as of 2006) incur some risk for developing cognitive dysfunction, with the most severe cases found in patients subjected to cranial radiotherapy (~200,000/yr) for the control of primary and metastatic brain tumors1. Particularly problematic are pediatric cases, whose long-term survival plagued with marked cognitive decrements results in significant socioeconomic burdens2. To date, there are still no satisfactory solutions to this significant clinical problem.
We have addressed this serious health concern using transplanted stem cells to combat radiation-induced cognitive decline in athymic rats subjected to cranial irradiation3. Details of the stereotaxic irradiation and the in vitro culturing and transplantation of human neural stem cells (hNSCs) can be found in our companion paper (Acharya et al., JoVE reference). Following irradiation and transplantation surgery, rats are then assessed for changes in cognition, grafted cell survival and expression of differentiation-specific markers 1 and 4-months after irradiation. To critically evaluate the success or failure of any potential intervention designed to ameliorate radiation-induced cognitive sequelae, a rigorous series of quantitative cognitive tasks must be performed. To accomplish this, we subject our animals to a suite of cognitive testing paradigms including novel place recognition, water maze, elevated plus maze and fear conditioning, in order to quantify hippocampal and non-hippocampal learning and memory. We have demonstrated the utility of these tests for quantifying specific types of cognitive decrements in irradiated animals, and used them to show that animals engrafted with hNSCs exhibit significant improvements in cognitive function3.
The cognitive benefits derived from engrafted human stem cells suggest that similar strategies may one day provide much needed clinical recourse to cancer survivors suffering from impaired cognition. Accordingly, we have provided written and visual documentation of the critical steps used in our cognitive testing paradigms to facilitate the translation of our promising results into the clinic.

Cognitive impairment resulting from the radiotherapeutic management of brain tumors represents a clinically intractable condition that adversely impacts quality of life. The capability to critically evaluate potential interventions for ameliorating radiation-induced cognitive decrements ultimately depends on the capability to undertake rigorous quantitative assessments of cognition.

Kranial Radyoterapi Yarattığı Bilişsel Azaltır nicel

With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For ...

Tıp

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer&#8217;s disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer&#8217;s disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences.

Morris Water Maze Testi: Fare Gerilme ve Test Ortamı için Optimizasyon

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

Morris Water Maze Experiment

The Morris water maze is widely used to study spatial memory and learning. Animals are placed in a pool of water that is colored opaque with powdered non-fat milk or non-toxic tempera paint, where they must swim to a hidden escape platform. Because they are in opaque water, the animals cannot see the platform, and cannot rely on scent to find the escape route. Instead, they must rely on external/extra-maze cues. As the animals become more familiar with the task, they are able to find the platform more quickly. Developed by Richard G. Morris in 1984, this paradigm has become one of the "gold standards" of behavioral neuroscience.

The Morris water maze is a well-accepted tool used to document the involvement of the hippocampus in a behavioral task.

Morris Su Labirent Deney

The Morris water maze is widely used to study spatial memory and learning. Animals are placed in a pool of water that is colored opaque with powdered ...

Biyoloji

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and validated for rat use. The Radial Water Tread (RWT) maze test of spatial memory (designed specifically for mice and requiring no swimming) has been shown previously to successfully distinguish between controlled cortical impact-induced TBI mice and sham controls. Here, a detailed protocol for this task is presented. The RWT maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the sides of an apparatus (thigmotaxis). The walls of the maze are lined with nine escape holes placed above the floor of the apparatus, and mice are trained to use visual cues to locate the escape hole that leads out of the maze. The maze is filled with an inch of cold water, sufficient to motivate escape but not deep enough to require that the mouse swim. The acquisition period takes only four training days, with a test of memory retention on day five and a long-term memory test on day 12. The results reported here suggest that the RWT maze is a feasible alternative to rat-validated, swimming-based cognitive tests in the assessment of spatial memory deficits in mouse models of TBI.

Here we present a protocol for a mouse-specific test of cognition that does not require swimming. This test can be used to successfully distinguish controlled cortical impact-induced traumatic brain injury mice from sham controls.

Radyal bir Su Basamalı Labirent Kullanarak Travmatik Beyin Hasarı Fare Modelinde Mekansal Bellek Bozukluğunu Değerlendirme

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and ...

Analysis of Learning and Memory Ability in an Alzheimer's Disease Mouse Model using the Morris Water Maze

A Morris water maze (MWM) experiment forces experimental animals to swim and learn to find a platform hidden in the water. It is widely used in scientific research to assess the learning and memory of animals. Due to the extensive use of the MWM test, visual experimental protocols are essential for researchers. This manuscript uses the latest studies to introduce the protocol of the MWM test. Alzheimer&#8217; Disease (AD) is characterized by a progressive loss of memory and cognitive function. An alternative and complementary treatment used for AD is Manual Acupuncture (MA). To assess the learning and memory ability of AD model mice, the MWM test was conducted. The visible platform trial, hidden platform trial, probe trial, and reversal trial of MWM were used to evaluate spatial learning and memory ability. In the visible platform trial, the swimming speed and escape latency of mice in different groups was not significantly different. In the hidden platform and reversal trials, the AD group showed a long escape latency. The escape latency decreased significantly after the MA treatment. Low platform crossover number and the proportion of time in the SW quadrant in the probe trial increased after the MA treatment (p &#60; 0.05 or p &#60; 0.01). The results of the MWM tests suggest that MA can effectively improve the spatial learning and memory abilities of AD model mice. Rigorous experimental operations provided assurance of the reliability of the results.

Herein, a protocol to conduct the Morris water maze tests to evaluate the ability of learning and memory of Alzheimer&#8217;s Disease model mice and to assess the effect of manual acupuncture for treating them is described.

Morris Su Labirenti Kullanarak Alzheimer Hastalığı Fare Modelinde Öğrenme ve Hafıza Yeteneğinin Analizi

A Morris water maze (MWM) experiment forces experimental animals to swim and learn to find a platform hidden in the water. It is widely used in scientific ...

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke.
For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

To investigate the co-morbid Alzheimer&#39;s disease (AD) and stroke condition in a novel model, three behavior tasks are described that assess both motor control and cognitive behaviors. These tasks include the beam-walk task, cylinder task and Morris water maze.

İnme ile Alzheimer Hastalığının bir Transgenik Fare Modelinde Motor ve Hipokampal Bağımlı Mekansal Öğrenme ve Referans Hafıza Değerlendirme

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

A Needle Model for Vascular Cognitive Impairment Studies in Mice

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis

Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID&#39;s high incidence, which is expected to continue rising as the population ages, it is critical to establish a robust animal model for the disease. This paper presents a novel method of creating a mouse model of VCID that is based on asymmetric bilateral common carotid artery stenosis, which mimics human chronic cerebral hypoperfusion caused by carotid atherosclerosis.
Briefly, common carotid arteries (CCAs) are ligated to different gauge needles (32 G for the right CCA and 34 G for the left CCA) using 7-0 silk sutures followed by immediate needle removal. The remaining suture rings cause persistent blood flow reduction and long-term cognitive impairment associated with white matter injury, microinfarcts, and reactive gliosis, thus closely mimicking the pathogenesis of VCID. Importantly, in this needle model, the clinical representations do not revert with time, providing reliable long-term cognitive impairment. Moreover, the survival rate 24 weeks post surgery was 81.6%, which is higher compared to the other established models of VCID with a similar level of blood flow reduction.
Additional advantages include low material cost and compatibility with MRI to monitor brain injury in live animals since no metal is implanted. The main challenge in employing the needle model of VCID is the requirement for developing advanced surgical skills since mouse CCAs are less than 0.6 mm in diameter and are very fragile. High-quality visual representation of the surgery will thus help researchers to master this technique and advance our understanding of VCID, potentially leading to the development of novel therapeutic modalities to decrease the devastating cognitive decline associated with VCID.

The needle method of asymmetric bilateral common carotid artery stenosis is proposed to create a mouse model for vascular cognitive impairment and dementia. It results in longer-term outcomes compared to previously established models and is compatible with live MRI. Visual representation demonstrating the procedure provides guidance for mastering the surgery.

Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID&#39;s high incidence, which is expected to continue ...

The Morris Water Maze

The Morris water maze is one of the most widely used behavioral tests for studying spatial learning and memory. In the initial phases of this task, rodents must swim to a platform to escape from a pool of water. The platform is then hidden under the water&#8217;s surface, so that the animal is required to remember it&#8217;s location in order to escape.This simple yet powerful maze design can be used to assay cognitive function, study animal models of neurodegenerative disease, and test potential drug therapies.
This video provides an introduction to the Morris water maze and the principles surrounding its use, including a discussion of the different types of memory tested in the maze, important points to consider when designing and conducting this experiment, and the procedures for setup and running of the test. Several applications of the maze are examined, such as investigating how radiation treatment may lead to memory impairment. Finally, other types of water mazes, such as the 8-arm radial maze, are introduced to show how this paradigm can be adapted to engage different types of memory.

The Morris water maze is one of the most widely used behavioral tests for studying spatial learning and memory. In the initial phases of this task, ...