מחקר זה נתמך על ידי מענק NIHM MH091816 R01 ו R21 MH084043 ל TDG.

<ol>
	<li>Hasco&#233;t, M., Bourin, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> In Mood and Anxiety Related Phenotypes in Mice. 42, 85-118 (2009).</li><li>Sunal, R., G&#252;m&#252;&#231;el, a. B., Kayaalp, S. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+changes+in+swimming+area+on+results+of+"behavioral+despair+test".">Effect of changes in swimming area on results of "behavioral despair test".</a> Pharmacology Biochemistry and Behavior. 49, 891-896 (1994).</li><li>Petit-Demouliere, B., Chenu, F., Bourin, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Forced+swimming+test+in+mice:+a+review+of+antidepressant+activity.">Forced swimming test in mice: a review of antidepressant activity.</a> Psychopharmacology. (Berl). 177, 245-255 (2005).</li><li>Cryan, J. F., Markou, A., Lucki, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+antidepressant+activity+in+rodents:+recent+developments+and+future+needs.">Assessing antidepressant activity in rodents: recent developments and future needs.</a> Trends in Pharmacological Sciences. 23, 238-245 (2002).</li><li>Can, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antidepressant-like+responses+to+lithium+in+genetically+diverse+mouse+strains.">Antidepressant-like responses to lithium in genetically diverse mouse strains.</a> Genes, Brain and Behavior. 10, 434-443 (2011).</li><li>Lucki, I., Dalvi, A., Mayorga, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensitivity+to+the+effects+of+pharmacologically+selective+antidepressants+in+different+strains+of+mice.">Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice.</a> Psychopharmacology. (Berl). 155, 315-322 (2001).</li><li>David, D. J., Renard, C. E., Jolliet, P., Hascoet, M., Bourin, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antidepressant-like+effects+in+various+mice+strains+in+the+forced+swimming+test.">Antidepressant-like effects in various mice strains in the forced swimming test.</a> Psychopharmacology (Berl). 166, 373-382 (2003).</li><li>Bai, F., Li, X., Clay, M., Lindstrom, T., Skolnick, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intra-+and+interstrain+differences+in+models+of+"behavioral+despair".">Intra- and interstrain differences in models of "behavioral despair".</a> Pharmacol. Biochem. Behav. 70, 187-192 (2001).</li><li>Guzzetti, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strain+differences+in+paroxetine-induced+reduction+of+immobility+time+in+the+forced+swimming+test+in+mice:+Role+of+serotonin.">Strain differences in paroxetine-induced reduction of immobility time in the forced swimming test in mice: Role of serotonin.</a> European Journal of Pharmacology. 594, 117-124 (2008).</li><li>Cervo, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genotype-dependent+activity+of+tryptophan+hydroxylase-2+determines+the+response+to+citalopram+in+a+mouse+model+of+depression.">Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression.</a> J. Neurosci. 25, 8165-8172 (2005).</li><li>Jiao, J., Nitzke, A., Doukas, D., Seiglie, M., Dulawa, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antidepressant+response+to+chronic+citalopram+treatment+in+eight+inbred+mouse+strains.">Antidepressant response to chronic citalopram treatment in eight inbred mouse strains.</a> Psychopharmacology. 213, 509-520 (2011).</li><li>Porsolt, R. D., Pichon, M. L. e., Jalfre, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Depression:+a+new+animal+model+sensitive+to+antidepressant+treatments.">Depression: a new animal model sensitive to antidepressant treatments.</a> Nature. 266, 730-732 (1977).</li><li>Porsolt, R. D., Bertin, A., Jalfre, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+despair+in+mice:+a+primary+screening+test+for+antidepressants.">Behavioral despair in mice: a primary screening test for antidepressants.</a> Arch. Int. Pharmacodyn. Ther. 229, 327-336 (1977).</li><li>Porsolt, R. D., Bertin, A., Jalfre, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term="Behavioural+despair"+in+rats+and+mice:+strain+differences+and+the+effects+of+imipramine.">"Behavioural despair" in rats and mice: strain differences and the effects of imipramine.</a> Eur. J. Pharmacol. 51, 291-294 (1978).</li><li>Mineur, Y. S., Belzung, C., Crusio, W. E. <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+unpredictable+chronic+mild+stress+on+anxiety+and+depression-like+behavior+in+mice.">Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice.</a> Behav. Brain. Res. 175, 43-50 (2006).</li><li>Millstein, R. A., Holmes, A. <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+repeated+maternal+separation+on+anxiety-+and+depression-related+phenotypes+in+different+mouse+strains.">Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains.</a> Neuroscience &#38; Biobehavioral Reviews. 31, 3-17 (2007).</li><li>Cryan, J. F., Valentino, R. J., Lucki, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+substrates+underlying+the+behavioral+effects+of+antidepressants+using+the+modified+rat+forced+swimming+test.">Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test.</a> Neuroscience &#38; Biobehavioral Reviews. 29, 547-569 (2005).</li><li>Crowley, J. J., Jones, O. '. L. e. a. r. y., F, O., Lucki, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+tests+for+measuring+the+effects+of+antidepressants+in+mice.">Automated tests for measuring the effects of antidepressants in mice.</a> Pharmacology Biochemistry and Behavior. 78, 269-274 (2004).</li><li>Kurtuncu, M., Luka, L. J., Dimitrijevic, N., Uz, T., Manev, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliability+assessment+of+an+automated+forced+swim+test+device+using+two+mouse+strains.">Reliability assessment of an automated forced swim test device using two mouse strains.</a> Journal of Neuroscience Methods. 149, 26-30 (2005).</li><li>Hayashi, E., Shimamura, M., Kuratani, K., Kinoshita, M., Hara, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+experimental+system+capturing+three+behavioral+components+during+murine+forced+swim+test.">Automated experimental system capturing three behavioral components during murine forced swim test.</a> Life Sciences. 88, 411-417 (2011).</li><li>Cryan, J., Page, M., Lucki, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+behavioral+effects+of+the+antidepressants+reboxetine,+fluoxetine,+and+moclobemide+in+a+modified+forced+swim+test+following+chronic+treatment.">Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment.</a> Psychopharmacology. 182, 335-344 (2005).</li><li>Gould, T. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beta-catenin+overexpression+in+the+mouse+brain+phenocopies+lithium-sensitive+behaviors.">Beta-catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviors.</a> Neuropsychopharmacology. 32, 2173-2183 (2007).</li><li>Can, A., Grahame, N. J., Gould, T. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Affect-related+related+behaviors+in+mice+selectively+bred+for+high+and+low+voluntary+alcohol+consumption.">Affect-related related behaviors in mice selectively bred for high and low voluntary alcohol consumption.</a> Behav. Genet. , (2011).</li><li>McKinney, W. T., Bunney, W. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+Model+of+Depression:+I+Review+of+Evidence:+Implications+for+Research..">Animal Model of Depression: I Review of Evidence: Implications for Research..</a> Arch. Gen. Psychiatry. 21, 240-248 (1969).</li><li>Willner, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+validity+of+animal+models+of+depression.">The validity of animal models of depression.</a> Psychopharmacology.(Berl). 83, 1-16 (1984).</li><li>Detke, M. J., Lucki, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+serotonergic+and+noradrenergic+antidepressants+in+the+rat+forced+swimming+test:+the+effects+of+water+depth.">Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth.</a> Behav. Brain Res. 73, 43-46 (1995).</li><li>Gould, T. D., Dao, D. T., Kovacsics, C. E., Gould, T. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> In Mood and Anxiety Related Phenotypes in mice: characterization using behavioral tests. 42, (2009).</li><li>Bourin, M., Fiocco, A. J., Clenet, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+valuable+are+animal+models+in+defining+antidepressant+activity.">How valuable are animal models in defining antidepressant activity.</a> Human Psychopharmacology: Clinical and Experimental. 16, 9-21 (2001).</li></ol>

המחברים מצהירים שום ניגוד אינטרסים.

FST (המכונה לעתים מבחן לשחות Porsolt) פותח לראשונה עבור חולדות שונה אז עבור העכברים על ידי Porsolt ועמיתיו 12,13. בנוסף פרוטוקול המתואר לעיל המוצלח במעבדה שלנו, מספר שינויים בעיקר מבחן עדין פורסמו (ראה Hascoët ו Bourin לסקירה מלאה 1). זהו מבחן הנפוצות להערכת היעילות של תרופות נגד דיכאון ואת ההשפעות של מניפולציות התנהגותיות הנוירוביולוגי שונים מחקר בסיסי פרה 3,14-16. היא תוארה בתור טיוח מצב שבו &quot;ייאוש התנהגותי&quot; מושרה, כלומר, החיה מאבדת תקווה להימלט סביבה מלחיצה 13. הגרסה עכבר הבדיקה נאלץ לשחות הוא מבחן עלות קצר יחסית נמוך התנהגות לא דורש הכשרה של העכברים והוא יכול להתבצע עם ציוד מינימלי. זאת בניגוד לגרסה עכברוש המבחן, אשר בדרך כלל כרוךהחשיפה של מיכל המים, יום אחד לפני יום המבחן 17. בגלל הפופולריות שלו יש שפע של נתונים על ההשפעות של תרופות נוגדות דיכאון שונות FST. הדבר מאפשר לחוקרים להשוות לעומת התוצאות שלהם עם אחרים (ראה Hascoët ו Bourin לבדיקה 2009 1). אלה המאפיינים של FST לעשות את זה כלי חשוב במחקר האקדמי גילוי סמים במסגרות תעשייתי שבו אמינות ההקרנה תפוקה גבוהה של תרכובות הרומן חיוניים. תכונה נוספת של FST הוא הזמינות של מסחר אוטומטיות ניתוח מערכות התנהגות שיכולה להאיץ את תהליך איסוף הנתונים 18-20. עם זאת, הניסיון שלנו, אלו מערכות אוטומטיות דורשים אימות נרחב כשקלע האדם. בנוסף, פרמטרים אוטומטית עשוי להיות וסידרה בעת שימוש זנים שונים, במיוחד כאשר רמת שינויים לעומת הרקע, או עם עכברים של ים שוניםizes או תגובות התנהגותיות. תחום נוסף שבו FST משמש הוא מחקר neurogenetic שבו הבסיס הגנטי של דיכאון הקשורים להתנהגויות נחקר. אלו סוגים של מחקרים לערב השוואה של זני עכברים שונים, עם או בלי שימוש בתרופות נגד דיכאון והשוואות של עכברים מהונדסים גנטית או גידל סלקטיבי עמיתיהם בטבע שלהם סוג 6,21-23. בהקשר זה, FST הוכיח להיות שימושי במחקר בסיסי הקשורים הנוירוביולוגיה והגנטיקה של הפרעות במצב הרוח. עם זאת, FST אינו אנלוגי ספקטרום מלא של דיכאון אנושי. למרות שיש יוצאים מן הכלל, FST יש רמה ניכרת של תוקף ניבוי, שכן הוא רגיש באופן סביר תרכובות יעילות בבני אדם כמו תרופות נגד דיכאון וחסר רגישות לאלה שאינם יעילים 24,25. מאז תוצאה התנהגותית של FST הוא חד ממדי זה יכול רק לציין את היעילות של תרופות נוגדות דיכאון או תרכובת לשעברמניפולציות perimental, אבל זה לא יכול להבחין בהבדלים מכניסטית ביניהם. זאת בניגוד לגירסה של עכברוש FST, שם חולדות לידי ביטוי הן שחייה טיפוס התנהגויות יכולים להבדיל בין סרוטונין ונוראפינפרין משחק תרכובות 26. כמו כן כל המניפולציות שעשויים להשפיע על רמת הפעילות הכוללת פוטנציאלי עלול לשנות תנועה ב FST המוביל למסקנות מזויף. לכן חשוב לבדוק את התוצאות של FST עם בדיקות התנהגותיות נפרד למדוד פעילות הכוללת כגון מבחן פתוח בתחום 1,27. זה מועיל לזכור כי FST אינו מייצג את המצב האנושי, ובמידה שבה מנגנוני הנוירוביולוגי הבסיסית של התנהגות המתבטאת חיות מודל החפיפה דיכאון FST האדם אינו ברור לחלוטין 28. עם זאת, אלו סוגים של מגבלות לא צריך פיחות את השימושיות של FST כתגלית סמים כלי האימות.

<ul style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> מיכלי מים </li><li style=";text-align:right;direction:rtl"> מדחום </li><li style=";text-align:right;direction:rtl"> שעון עצר </li><li style=";text-align:right;direction:rtl"> מצלמת וידיאו </li><li style=";text-align:right;direction:rtl"> מחולל רעש לבן (אופציונלי) </li><li style=";text-align:right;direction:rtl"> ייבוש נייר </li></ul>

the mouse forced swim test

המבחן נאלץ לשחות הוא מבחן התנהגותי מכרסם המשמש להערכה של תרופות נוגדות דיכאון, נוגדות דיכאון יעילות של תרכובות חדשות, ומניפולציות הניסוי מכוונים טיוח או מניעת דיכאון, כמו מדינות. עכברים ממוקמים מיכל שקוף שאין מנוס ממנו כי הוא מלא מים הקשורים בריחתם התנהגות ניידות נמדד. המבחן נאלץ לשחות היא פשוטה לנהל אמין זה דורש ציוד מיוחד מינימלית. יישום מוצלח של הבדיקה נאלץ לשחות דורש דבקות פרטים פרוצדורליים מסוימים וצמצום מתח מוצדקת על עכברים. בתיאור פרוטוקול הווידאו הנלווה, נסביר כיצד לנהל את הגרסה העכבר של מבחן זה, עם דגש על בעיות פוטנציאליות שעלולות להזיק הפרשנות של התוצאות וכיצד להימנע מהם. בנוסף, אנו מסבירים כיצד התנהגויות לידי ביטוי במבחן מוערכים.

Watch this Scientific Journal Video about The Mouse Forced Swim Test at JoVE.com

The Mouse Forced Swim Test

המבחן הוא נאלץ לשחות תוקף כגישה הניסוי להעריך את יעילות נגד דיכאון פוטנציאל במכרסמים. חיות הניסוי ממוקמות בתוך טנק מים לברוח בנושא התנהגות ניידות לכימות. הנהלים משותף לגרסה העכבר של מבחן זה מתוארים.

עכבר בכפייה לשחות מבחן

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

Nanyang Technological University

Research

JoVE Journal

Neuroscience

105.1K Views.  University of Maryland School of Medicine. המבחן הוא נאלץ לשחות תוקף כגישה הניסוי להעריך את יעילות נגד דיכאון פוטנציאל במכרסמים. חיות הניסוי ממוקמות בתוך טנק מים לברוח בנושא התנהגות ניידות לכימות. הנהלים משותף לגרסה העכבר של מבחן זה מתוארים.

Video: The Mouse Forced Swim Test

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.

מים רדודים (חתירה) נוסחים שונים של בדיקות מבוך מים בעכברים

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 ...

Behavior

The Forced Swim Test as a Model of Depressive-like Behavior

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

המבחן לשחות בכפייה כמודל להתנהגות דמוית דיכאון

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like ...

Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown gene expression in a relatively focused region without significant damage to the brain tissue. After recovery, the injected mouse can be tested on various behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice by measuring the amount of time that a mouse spends in the center of a novel open field. A more anxious mouse will spend significantly less time in the center of the novel field compared to controls. The FST assesses the anti-depressive phenotype by quantifying the amount of time that mice spend immobile when placed into a bucket of water. A mouse with an anti-depressive phenotype will spend significantly less time immobile compared to control animals. The goal of this protocol is to use the stereotactic injection of a lentivirus in conjunction with behavioral tests to assess how genetic factors modulate animal behaviors.

Stereotactic injection of lentiviruses expressing cDNAs or shRNAs can modulate gene expression in specific brain areas of mice. Here, we present a protocol to combine stereotactic injections with behavioral tasks, such as the Open Field Test (OFT) and the Forced Swim Test (FST).

יישום טכניקת הזרקת stereotactic לחקר השפעות גנטיות על התנהגות בעלי החיים

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or ...

The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their behavioral flexibility and required memory duration, the number of goals and pathways, and also the overall task complexity. A confounding feature in many of these tasks is the lack of control over the strategy employed by the rodents to reach the goal, e.g., allocentric (declarative-like) or egocentric (procedural) based strategies. The double-H maze is a novel water-escape memory task that addresses this issue, by allowing the experimenter to direct the type of strategy learned during the training period. The double-H maze is a transparent device, which consists of a central alleyway with three arms protruding on both sides, along with an escape platform submerged at the extremity of one of these arms.
Rats can be trained using an allocentric strategy by alternating the start position in the maze in an unpredictable manner (see protocol 1; &#167;4.7), thus requiring them to learn the location of the platform based on the available allothetic cues. Alternatively, an egocentric learning strategy (protocol 2; &#167;4.8) can be employed by releasing the rats from the same position during each trial, until they learn the procedural pattern required to reach the goal. This task has been proven to allow for the formation of stable memory traces.
Memory can be probed following the training period in a misleading probe trial, in which the starting position for the rats alternates. Following an egocentric learning paradigm, rats typically resort to an allocentric-based strategy, but only when their initial view on the extra-maze cues differs markedly from their original position. This task is ideally suited to explore the effects of drugs/perturbations on allocentric/egocentric memory performance, as well as the interactions between these two memory systems.

The goal of this protocol is to investigate spatial cognition in rodents. The double-H water maze is a novel test, which is particularly useful to elucidate the different components of learning, consolidation and memory, as well as the interplay of memory systems.

זוגי H-המבוך: מבחן חזק התנהגות למידה וזיכרון במכרסמים

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their ...

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.

מבחן מוריס מים מבוך: אופטימיזציה לזני עכבר ובדיקת איכות סביבה

 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 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'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.

מוריס מבוך המים מבחן גירעונות למידה וזיכרון במודל של מחלת אלצהיימר עכברים

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

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

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of &alpha;-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that &alpha;-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that &alpha;-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

This article presents the protocol of T-maze tests using a modified automated apparatus for assessing the learning and memory functions in mice.

T-מבוך לסירוגין בכפייה של שמאל וימין משימות אפליה להערכת עבודה וזיכרון העזר עכברים

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

The Tail Suspension Test

The tail-suspension test is a mouse behavioral test useful in the screening of potential antidepressant drugs, and assessing of other manipulations that are expected to affect depression related behaviors. Mice are suspended by their tails with tape, in such a position that it cannot escape or hold on to nearby surfaces. During this test, typically six minutes in duration, the resulting escape oriented behaviors are quantified. The tail-suspension test is a valuable tool in drug discovery for high-throughput screening of prospective antidepressant compounds. Here, we describe the details required for implementation of this test with additional emphasis on potential problems that may occur and how to avoid them. We also offer a solution to the tail climbing behavior, a common problem that renders this test useless in some mouse strains, such as the widely used C57BL/6. Specifically, we prevent tail climbing behaviors by passing mouse tails through a small plastic cylinder prior to suspension. Finally, we detail how to manually score the behaviors that are manifested in this test.

The tail-suspension test is validated as an experimental procedure to assess antidepressant efficacy of drug treatments in mice. Mice are suspended by their tails for six minutes and escape-related behaviors are assessed. We describe procedures used in conducting the tail suspension test.

השעיה זנב מבחן

The tail-suspension test is a mouse behavioral test useful in the screening of potential antidepressant drugs, and assessing of other manipulations that ...

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.

סוללה בדיקה התנהגותית להערכה חוזרת ונשנית של מיומנויות מוטוריות, מצב רוח, קוגניציה בעכברים

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

The Mouse Stroke Unit Protocol with Standardized Neurological Scoring for Translational Mouse Stroke Studies

The filament model of middle artery occlusion (fMCAo) is perhaps the most translational mouse stroke model, allowing for controlled ischemia with intravascular reperfusion/recanalization. However, it lacks alignment with current clinical advances for stroke care (e.g., Stroke Units), usually employs subjective or vague neurological scoring among laboratories, and exhibits high acute-phase mortality. Here, we address these limitations with validated video-guided protocols. We present the mouse Stroke Unit (mSU) protocol with instructional videos and a decision algorithm (Risk Stratification Score), bridging the gap between clinical and mouse stroke modeling. To increase accuracy and sensitivity of stroke neurological scoring, we present for the first time a video-standardized format of the focal Experimental Stroke Scale (fESS) and prove its value up to 6 months post-stroke. Additionally, protocols for mice Ladder-rung test, as well as the known Cylinder test, for unbiased, quantitative assessment of limbs&#180; motor function are presented. Results highlight mSU&#39;s translational efficacy. Focal ESS (fESS) excels over other known scales in detecting focal stroke deficits, capturing recovery, and maintaining sensitivity for up to 6 months post-stroke. Ladder-rung and Cylinder tests objectively quantify and monitor fore- and hind-limb motor deficits, long-term. In summary, integrating mSU, fESS, and motor function tests provides a robust framework for clinically relevant stroke investigations. Our protocols improve the translational value in mouse stroke research.

This article presents a protocol for executing the highly translational and independently proven mouse Stroke Unit (mSU) concept in large-stroke mice. It also provides a standardized protocol for executing the focal experimental stroke scale in mice, which evaluates stroke focal deficits detected even long-term.