、神経疾患·脳卒中研究所（アッシュ - R01NS33249、R01NS63249とR01NS79374）、CoBRE（エングラー-Chiurazzi - P20GM109098）、 - この作品は、一般医科学研究所（U54GM104942リード/エングラー-Chiurazzi）によってサポートされていましたアルツハイマー病協会（リード - NIRG-12から242187）、WVU学部研究上院グラント（リード）、医学ディーンのオフィスのWVU大学（エングラー-Chiurazzi）からWVU PSCORグラント（リード）、および内部資金。内容はもっぱら著者の責任であり、必ずしもNIHやアルツハイマー病協会の公式見解を示すものではありません。

<ol>
	<li>Ramsden, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-dependent+neurofibrillary+tangle+formation,+neuron+loss,+and+memory+impairment+in+a+mouse+model+of+human+tauopathy+(P301L).">Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L).</a> The Journal of Neuroscience. 25, 10637-10647 (2005).</li><li>Attar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+shortened+barnes+maze+protocol+reveals+memory+deficits+at+4-months+of+age+in+the+triple-transgenic+mouse+model+of+Alzheimer's+disease.">A shortened barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease.</a> PLoS One. 8, e80355 (2013).</li><li>Johnson, J. M., Bailey, J. 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A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+between+abeta+and+memory+in+the+Tg2576+mouse+model+of+Alzheimer's+disease.">The relationship between abeta and memory in the Tg2576 mouse model of Alzheimer's disease.</a> The Journal of Neuroscience. 22, 1858-1867 (2002).</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>Santa Cruz, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tau+suppression+in+a+neurodegenerative+mouse+model+improves+memory+function.">Tau suppression in a neurodegenerative mouse model improves memory function.</a> Science. 309, 476-481 (2005).</li><li>Hunsberger, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+size+of+memory+deficits+in+mice+with+adult-onset+P301L+tau+expression.">Effect size of memory deficits in mice with adult-onset P301L tau expression.</a> Behavioural Brain Research. 272, 181-195 (2014).</li><li>Yue, M., Hanna, A., Wilson, J., Roder, H., Janus, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sex+difference+in+pathology+and+memory+decline+in+rTg4510+mouse+model+of+tauopathy.">Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy.</a> Neurobiology of Aging. 32, 590-603 (2011).</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 plasticity. 6, 41-52 (1998).</li><li>H&#246;lscher, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=C.+impairs+performance+in+spatial+water+maze+learning+tasks.">C. impairs performance in spatial water maze learning tasks.</a> Behavioural Brain Research. 100, 225-235 (1999).</li><li>Morris, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developments+of+a+water-maze+procedure+for+studying+spatial+learning+in+the+rat.">Developments of a water-maze procedure for studying spatial learning in the rat.</a> Journal of Neuroscience Methods. 11, 47-60 (1984).</li><li>Reed, M. N., Liu, P., Kotilinek, L. A., Ashe, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+size+of+reference+memory+deficits+in+the+morris+water+maze+in+Tg2576+mice.">Effect size of reference memory deficits in the morris water maze in Tg2576 mice.</a> Behavioural Brain Research. 212, 115-120 (2010).</li><li>Huang, Y., Zhou, W., Zhang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bright+lighting+conditions+during+testing+increase+thigmotaxis+and+impair+water+maze+performance+in+BALB/c+mice.">Bright lighting conditions during testing increase thigmotaxis and impair water maze performance in BALB/c mice.</a> Behavioral Brain Research. 226, 26-31 (2012).</li><li>Ivonen, H., Nurminen, L., Harri, M., Tanila, H., Puolivali, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypothermia+in+mice+tested+in+Morris+water+maze.">Hypothermia in mice tested in Morris water maze.</a> Behavioural Brain Research. 141, 207-213 (2003).</li><li>Rubinow, M. J., Arseneau, L. M., Beverly, J. L., Juraska, J. M. <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+estrous+cycle+on+water+maze+acquisition+depends+on+the+temperature+of+the+water.">Effect of estrous cycle on water maze acquisition depends on the temperature of the water.</a> Behavioral Neuroscience. 118 (4), 863-868 (2004).</li></ol>

著者らは、開示することは何もありません。

MWMタスクが広く、空間学習および記憶を評価するために使用されます。しかし、このタスクの堅牢性は、多くの要因によって影響を受け、バックグラウンド株とテスト環境の両方の最適化を必要とすることができます。 図4に示すように、同一の訓練プロトコルおよび2つの異なる検査室（同等のサイズとレイアウト）に使用される視覚的な手がかりを印加は有意に異なるプロー?...

トランスジェニックマウスモデルは、アルツハイマー病（AD）の病態、ならびに治療的介入の可能性を評価することに尽力しています。そのようなモリス水迷路（MWM）として認知タスクは、一般に記憶欠損の分子相関を識別し、前臨床薬物の有効性を評価するために、これらのモデルを使用しています。これは、認知タスクのダイナミックレンジは、微妙な治療効果を検出するのに十分な幅であることが重要です。 ADのマウスモデルでは、認知障害は、典型的には、年齢依存しており、マウスは、性能の漸進的減少を表示する（ 例えば 、1）。敏感な認知課題を使用すると、それによって老化動物に関連するコストを削減、以前の動物の生活の中で微妙な違いの検出を可能にすることができます。例えば、15から5海馬依存性バーンズ迷路訓練の試行回数を減らすことは、Dが得られ、作業の難易度を増加させより早い年齢で3xTgモデルの欠損のetectionは、以前に2を報告しました。赤字の早期発見だけでなく、それはまた、認知障害の根底にある分子変化を識別することができる可能性を高める、かなりの時間とコストの節約を提供しています。 認知タスクの感度に影響を与える要因の一つは、マウスモデルの遺伝的バックグラウンド株です。例えば、BALB / cマウスは、C57BL / 6 3などの他の株と比較して、学習および記憶課題における優れた性能を発揮します。 F1 FVB / N X 129S6バックグラウンドは、ADの最も広く使用されているモデル、のTg2576及びRTG（TauP301L）4510モデルの2のために使用されます。この株は、B6 / SJLマウス4を含む他の株にMWMの相対性に優れた学習能力を発揮します。このため、優れた学習能力の、広範囲の訓練の後に単一のプローブを使用することは、オーバートレーニングに起因するグループ間の相違を隠蔽することができます。また、sensitivitプローブ試行のyは年齢依存性であってもよいです。我々は以前、以前のプローブ試験は、限定され隠されたプラットフォームの訓練の後、より広範囲の訓練5の後に挿入されたプローブの試験よりも若い導入遺伝子陰性同腹子対照と比較して、若いのTg2576の違いに敏感であることが示されています。これとは対照的に、広範囲の訓練以下のプローブ試験は、以前のプローブ試験5以上経過した同腹仔と比較して、より古い（20〜25月）Tg2576マウスにおいて、より敏感です。長手方向のテストが実行され、特定のプローブの試験の感度は年齢に依存している場合は特に、トレーニングを通じてプローブ試行を散在することにより、敏感な試験が特定される可能性が増加する。1 F1 FVB / N xの優れた性能を示しより広範な訓練を受けたプロトコルの下で訓練を受けたB6 / SJLバックグラウンドのマウスに比べて、この株のために最適化されたプロトコルの下で129S6マウス。 MWMは、一般的に、時間と研究室6の両方で再現可能で信頼性の高い手段を提供すると考えられて。例えば、もともと私たちのミネソタ州の研究室の1,7で使用される主なプロトコルが正常にウェストバージニア大学8でマイナーな修正を加えて実施されました。同様に、障害の同等のレベルが病原体を含まない、または従来の条件9で飼育場合同腹子を制御するために、4510マウスの相対RTG（TauP301L）で観察されました。しかし、テスト環境は、MWMタスクの感度に影響を与えることができます。このような部屋の照明などの要因、空気口、温度勾配、および騒音すべては最終的に、パフォーマンスに影響を与えることができる環境の合図4に貢献しています。私たちのミネソタ州の研究室やビバリウムが新しい建物に移動した場合には、アップ野生型性能の38％の減少には、実質的にタスクと導入遺伝子関連の障害を検出する能力のダイナミックレンジを低減し、観察されました。 PEの変化rformanceは、同等のサイズと構成であることが試験室を設計し、同じ印加視覚的な手がかりを使用しているにもかかわらず発生しました。元のプロトコルの「再最適化は、「新たなテスト環境でMWMタスクのダイナミックレンジを増大させるために必要でした。 ここでF1 FVB / Nでの使用に合わせたオリジナルのプロトコルは、129S6の背景5が記載されているxは。いくつかの研究は、ストレスを示唆しているため、パフォーマンス11にこのストレス誘導赤字を緩和することができる貧しいMWMのパフォーマンス10および前処理に関連している、前処理プロトコルは、プールの導入および除去の前MWM試験のにマウスを順応するように設計されました。前処理後、マウスを上げプラットフォームはフラグでマークされている可視の足場訓練を受けます。可視の足場訓練は、感覚異常に関連するパフォーマンス問題を有するマウスを識別するために使用されます。 PROTに記載の除外基準を使用してocolセクション、パフォーマンス·無能なマウスは、隠されたプラットフォームのトレーニングおよびプローブ試験のその後の検査から削除されます。感覚性能はデータのうち因数分解されるため、隠されたプラットフォームのトレーニングとプローブ試験で障害が認知障害として解釈されます。可視の足場訓練の完了後、マウスに、プラットフォームを水に沈め、外部合図に同じ位置に残る隠れ足場訓練を開始します。プラットフォームが除去された試験（プローブトライアル）は、付加的な訓練の影響を評価するために、隠れプラットフォーム訓練を通して散在しています。プローブ試験は、毎日の開始時に発生するため、追加的な隠れ足場訓練の前に、プローブ試験は20時間の遅延の後にプラットフォームの位置を記憶する動物の能力を測定し、基準メモリ12の測定値を検討しました。最後に、方法は、このオリジナルのプロトコルは、再最適化されたときに、テスト環境の変化破壊された制御性能が記載されています。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Viewer Tracking software</td>
			<td>Biobserve</td>
			<td></td>
			<td>This particular software is not a requirement - there are other tracking systems available</td>
		</tr>
		<tr>
			<td>Pre-handling pool</td>
			<td></td>
			<td></td>
			<td>Dimensions approximately 1 foot wide x 2 feet long x 1.5 feet deep</td>
		</tr>
		<tr>
			<td>Plastic beaker</td>
			<td></td>
			<td></td>
			<td>1 liter</td>
		</tr>
		<tr>
			<td>Scoop</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Small net</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Stopwatch</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>White circular tub</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Non-toxic white tempera paint</td>
			<td></td>
			<td></td>
			<td>Any color can paint can be used; must completely cover the hidden platform</td>
		</tr>
		<tr>
			<td>Platform</td>
			<td></td>
			<td></td>
			<td>Color should contrast that of maze</td>
		</tr>
		<tr>
			<td>Curtain rod</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Curtains</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Mouse performance tracking software</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Circular tub</td>
			<td></td>
			<td></td>
			<td>Uusally white in color; approximately 4 feet in diamater</td>
		</tr>
		<tr>
			<td>Platform</td>
			<td></td>
			<td></td>
			<td>Painted same color as the water</td>
		</tr>
	</tbody>
</table>

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.

我々は、 図3は 、β-アミロイド（Tg2576マウス）および変異P301Lタウ空間参照メモリ上（RTG（TauP301L）4510マウス）（ 例えば 、1,5,7,8）。の効果を研究するためにモリス水迷路を使用していました我々の研究で報告された代表的な結果をモータと視覚的能力を評価するためのテスト環境Aを利用して、学習と記憶8の成人発症P301Lタウ発現の効果を調べる、マウス?...

Watch this Scientific Journal Video about Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment at JoVE.com

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

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.

モリス水迷路試験：マウス系統およびテスト環境の最適化

 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-optimization-for-mouse-strain-testing

Research

JoVE Journal

Behavior

21.3K ビュー.  West Virginia University.  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. 

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

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.

マウスの水迷路試験の浅い水（スパンキング）バリアント

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 ...

行動学

Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury

Working and reference memory are commonly assessed using the land based radial arm maze.&#160;However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs.

新生児脳損傷後の作業とリファレンス記憶を評価〜8アーム放射状水迷路の使用

Working and reference memory are commonly assessed using the land based radial arm maze.&#160;However, this paradigm requires pretraining, food ...

Barnes Maze Testing Strategies with Small and Large Rodent Models

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

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

小型·大齧歯類モデルとバーンズ迷路テスト戦略

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

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.

ダブルH迷路：げっ歯類での学習と記憶のための堅牢な行動試験

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 ...

A Protocol for Housing Mice in an Enriched Environment

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of &#8216;toys&#8217; to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer.

Environmental enrichment for mice requires a complex and challenging setup, as well as comprehensive husbandry and handling techniques to assure robust metabolic and anti-cancer effects in the mice. This protocol provides detailed procedures to reproduce the above mentioned effects in mice.

豊かな環境の住宅マウス用のプロトコル

Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

トレッドミル疲労試験：マウスの​​疲労のような挙動のシンプルな、ハイスループットアッセイ

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

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.

半径方向水迷路迷路を用いた外傷性脳損傷のマウスモデルにおける空間記憶障害の評価

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

Testing Animal Anxiety in Rats: Effects of Open Arm Ledges and Closed Arm Wall Transparency in Elevated Plus Maze Test

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral science, conflicting outcomes are often provided from different laboratories. To identify reasons for the different outcomes, we previously focused on arm features, which differ between laboratories, most notably the presence/absence of ledges at the sides of open arms and the transparency/opaqueness of closed arm walls. In a previous report, we used a custom designed container to compare rat behavior on different combinations of open and closed arm designs under otherwise identical experimental conditions, and showed that differences in arm features interfere with experimental outcomes. In brief, open arm ledges significantly increased anxiety-like behavior in rats, while transparent arms may also have decreased this behavior. Furthermore, we verified a higher detection sensitivity of the effect of an anxiolytic drug in a combination of no-ledged open arm + opaque walled closed arm compared with a combination of ledged open arm + transparent walled closed arm. In this report, we introduce our protocol for the elevated plus maze test, together with discussion of the key results from the previous report and our experimental experience. We believe this report will provide useful information for researchers who have employed or who plan to use the elevated plus maze in their studies.

Rats' anxiety-like behavior tested by the elevated plus maze varies highly depending on the testing environment. Here we show how apparatus settings, especially arm structure, affect behavior on the maze, and we explain a reliable protocol to detect effects of anxiolytic drugs. This report will contribute to anxiety research.

ラットにおける動物の不安をテスト: 腕が開いて棚とクローズド アームの効果壁透明性高架十字迷路試験

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral ...

Testing for Metacognitive Responding Using an Odor-based Delayed Match-to-Sample Test in Rats

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, numerous behavioral tasks have been created, many of which utilize an option to decline memory tests. To assess metamemory in rats, we utilized this decline-test option paradigm by adapting previous visual delayed-match-to-sample tests (DMTS)1,2 developed for primate species to an odor-based test suitable for rodents. First,&#160;rats are given a sample to remember by digging in a cup of scented sand. After a delay, the rat is presented with four distinctly scented cups, one of which contains the identical scent experienced during the sample; if this matching cup is selected, then the rat obtains a preferred, larger reward. Selection of any of the other three non-matching sand-filled scented cups results in no reward. Retention intervals are individually titrated such that subjects perform between 40 and 70% correct, therefore ensuring rats sometimes remember and sometimes forget the sample. Here, the operational definition of metamemory is the ability to distinguish between the presence and absence of memory through behavioral responding. Towards this end, on two-thirds of trials, a decline option is presented in addition to the four choice cups (choice trials). If the decline-test option- an unscented colored sand cup, is selected, the subject receives a smaller less-preferred reward and avoids the memory test. On the remaining third of trials, the decline-test option is not available (forced trials), causing subjects to guess the correct cup when the sample is forgotten. On choice tests, subjects that know when they remember should select the decline option when memory is weak rather than take the test and choose incorrectly. Therefore, significantly higher performance on chosen tests as compared to forced memory tests is indicative of the adaptive use of the decline-test response and metacognitive responding.

This protocol describes a method for investigating the possibility of metamemory, or memory awareness, in rodents. The odor-based delayed-matching-to-sample paradigm is a novel, ecologically-relevant behavioral test useful for determining the extent to which rodents can adaptively respond based on cognitively monitoring the strength of their memory states.

ラットにおける試合のサンプル テストを延期臭ベースを使用してメタ認知的応答のテスト

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, ...

Measuring Active and Passive Tameness Separately in Mice

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two behavioral components: a reluctance to avoid humans (passive tameness) and a motivation to approach humans (active tameness). To quantify these components in mice, we previously developed behavioral tests for active tameness, passive tameness, and the willingness to stay on a human hand, each designed to be completed within 3 min. The data obtained were used for selective breeding, with a large number of mice analyzed per generation. The active tameness test measures the movement of the mouse toward a human hand and the contact it engages in. The passive tameness test measures the duration of time that a mouse tolerates human touch. In the stay-on-hand test, a mouse is placed on a human hand and touched slowly using the thumb of that hand; the duration of time that the animal remains on the hand is measured. Here, we describe the test set-up and apparatus, explain the procedures, and discuss the appropriate data analysis. Finally, we explain how to interpret the results.

Tameness in animals includes a reduction of avoidance responses to humans (passive tameness) and an increase in active approaches to humans (active tameness). Here, we describe detailed protocols for three behavioral tests (active tameness, passive tameness, and stay-on-hand tests) to separately measure the active and passive tameness of mice.

マウスで個別にアクティブとパッシブのふがいなさを測定

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two ...