Questo lavoro è stato sostenuto dal National Institute of scienze mediche generali (Reed / Engler-Chiurazzi - U54GM104942), l&#39;Istituto nazionale per i disordini neurologici e Stroke (Ashe - R01NS33249, R01NS63249 e R01NS79374), Cobre (Engler-Chiurazzi - P20GM109098), il Associazione Alzheimer (Reed - NIRG-12-242187), un WVU Faculty Research Senato Grant (Reed), una borsa di WVU PSCOR (Reed), e fondi interni del WVU College of Ufficio Medicina Dean (Engler-Chiurazzi). Il contenuto è di esclusiva responsabilità degli autori e non rappresentano necessariamente il punto di vista ufficiale della NIH o Associazione Alzheimer.

<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. M., Johnson, J. E., Newland, M. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Performance+of+BALB/c+and+C57BL/6+mice+under+an+incremental+repeated+acquisition+of+behavioral+chains+procedure.">Performance of BALB/c and C57BL/6 mice under an incremental repeated acquisition of behavioral chains procedure.</a> Behavioural Processes. 84, 705-714 (2010).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> What's wrong with my Mouse Behavioral phenotyping of transgenic and knockout mice. , 94-95 (2000).</li><li>Westerman, M. 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>

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Il compito MWM è ampiamente utilizzato per valutare l&#39;apprendimento spaziale e la memoria. Tuttavia, la robustezza di questo compito può essere influenzata da molti fattori e richiede l&#39;ottimizzazione sia bassa tensione e ambiente di prova. Come mostrato in figura 4, lo stesso protocollo di allenamento e applicata indicazioni visive utilizzate in due diverse camere di prova (dimensione equivalente e layout) ceduto prestazioni della sonda significativamente differenti. Dal momento che molte car...

Modelli di topi transgenici sono stati strumentali nel valutare la fisiopatologia della malattia di Alzheimer (AD), così come il potenziale di interventi terapeutici. Compiti cognitivi, come la Morris water maze (MWM), sono comunemente usati con questi modelli per identificare i correlati molecolari di deficit di memoria e per valutare l&#39;efficacia dei farmaci pre-clinici. È essenziale, tuttavia, che la gamma dinamica del compito cognitivo essere sufficientemente ampia per rilevare gli effetti del trattamento sottili. Con i modelli murini di AD, deficit cognitivi sono tipicamente età-dipendente, e topi mostrano cali progressivi in termini di prestazioni (ad esempio, 1). L&#39;uso di un compito cognitivo sensibile può consentire l&#39;individuazione di sottili differenze presto nella vita dell&#39;animale, riducendo in tal modo i costi associati con gli animali di invecchiamento. Ad esempio, riducendo il numero di prove di formazione nei Barnes ippocampali-dipendente labirinto 15-5 aumentato la difficoltà del compito, conseguente detection dei deficit nel modello 3xTg in età prima di quanto precedentemente riportato 2. In precedenza il rilevamento dei deficit non solo offre un notevole risparmio di tempo e di costi, ma aumenta anche la probabilità che i cambiamenti molecolari alla base deficit cognitivi possono essere identificati. Un fattore che influenza la sensibilità di compiti cognitivi è lo sfondo ceppo genetico del modello di topo. Ad esempio, topi BALB / c mostrano prestazioni superiori in compiti di apprendimento e memoria rispetto ad altri ceppi, quali la C57BL / 6 3. La F1 FVB / N x 129S6 sfondo viene utilizzato per due dei modelli più ampiamente utilizzati di AD, la Tg2576 e RTG (tauP301L) 4510 modelli. Questo ceppo presenta capacità di apprendimento superiore nel MWM rispetto ad altri ceppi, tra cui B6 / mice SJL 4. A causa di questa capacità di apprendimento superiore, l&#39;uso di una singola sonda dopo una formazione può mascherare differenze di gruppo derivanti da un&#39;eccessiva formazione. Inoltre, la sensibility di prove della sonda può essere età-dipendente. Abbiamo precedentemente dimostrato che i processi sonde precedenti, dopo l&#39;allenamento piattaforma nascosta limitato, sono più sensibili alle differenze di giovane Tg2576 rispetto ai giovani transgene-negativi controlli littermate che sono prove di sonda inserita dopo una formazione più ampia 5. Al contrario, le prove della sonda di seguito una formazione sono più sensibili a più anziani (20-25 mesi) i topi Tg2576 rispetto ai fratellini di età superiore ai sei precedenti prove sonda 5. Con inframmezzando prove sonda tutta la formazione, la probabilità che sarà identificato un processo sensibile è aumentata, in particolare se il test viene eseguito longitudinale e la sensibilità di un particolare processo sonda è dipendente dall&#39;età. La figura 1 mostra le prestazioni superiori di F1 FVB / N x topi 129S6 sotto il protocollo ottimizzato per questo ceppo rispetto a topi dello sfondo B6 / SJL addestrato sotto un protocollo con una formazione più ampia. La MWM ègeneralmente si pensa di fornire misure affidabili e riproducibili attraverso tempo e laboratori 6. Ad esempio, il protocollo principale originariamente utilizzato dal nostro laboratorio 1,7 Minnesota è stato implementato con successo con piccole modifiche alla West Virginia University 8. Allo stesso modo, i livelli equivalenti di impairment sono stati osservati in RTG (tauP301L) 4510 topi rispetto al controllo littermates se alloggiati in condizioni esenti da organismi patogeni o convenzionali 9. Tuttavia, l&#39;ambiente di test può influenzare la sensibilità del compito MWM. Fattori come l&#39;illuminazione della stanza, prese d&#39;aria, gradienti di temperatura, e rumori contribuiscono a stimoli ambientali 4 che alla fine possono influenzare le prestazioni. Quando il nostro laboratorio di Minnesota e vivaio sono stati spostati in un nuovo edificio, fino ad una riduzione del 38% nelle prestazioni wild-type è stata osservata, riducendo sostanzialmente la gamma dinamica del compito e la capacità di individuare i deficit transgene-related. Questo cambiamento di performance si è verificato nonostante progettazione della sala prove per essere di dimensione e configurazione equivalente, e con le stesse indicazioni visive applicate. A &quot;ri-ottimizzazione&quot; del protocollo originale era necessaria per aumentare la gamma dinamica del compito MWM nel nuovo ambiente di test. Qui il protocollo originale adatti per essere utilizzati con la F1 FVB / N x 129S6 fondo 5 è descritto. Poiché alcuni studi suggeriscono stress è associato con scarso rendimento MWM 10 e pre-trattamento può alleviare il deficit indotta da stress in prestazioni 11, un protocollo di pre-trattamento è stato progettato per acclimatare i topi per l&#39;introduzione e la rimozione della piscina prima della prova MWM . A seguito di pre-trattamento, i topi sottoposti a una formazione piattaforma visibile, in cui una piattaforma rialzata è contrassegnato da una bandiera. Formazione piattaforma Visibile è usato per identificare i topi con problemi di performance legati ad anomalie senso-motorie. Utilizzando criteri di esclusione di cui alla protsezione ocol, topi prestazioni incompetente vengono rimossi dalle successive esami di prove di formazione piattaforma e sonda nascosti. Le svalutazioni negli studi di formazione piattaforma e sonda nascosti vengono interpretati come deficit cognitivi perché le prestazioni sensomotoria è scomposto fuori dei dati. Dopo il completamento della formazione piattaforma visibile, topi cominciano formazione piattaforma nascosta in cui la piattaforma è immerso in acqua e rimane nella stessa posizione rispetto a stimoli esterni. Prove in cui la piattaforma viene rimosso (prove sonda) si alternano per tutta la formazione piattaforma nascosta per valutare l&#39;influenza di formazione supplementare. Poiché prove sonda verificano all&#39;inizio di ogni giorno, prima formazione aggiuntiva piattaforma nascosta, prove sonde misurano la capacità dell&#39;animale di ricordare la posizione della piattaforma seguito di un ritardo di 20 ore, considerata una misura di memoria di riferimento 12. Infine, i modi in cui questo protocollo originale era di ri-ottimizzate quando le variazioni di ambiente di testprestazioni di controllo perturbato sono descritti.

<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.

Abbiamo usato il Morris water maze per studiare gli effetti del beta-amiloide (Tg2576 topi) e mutanti P301L tau (RTG (tauP301L) 4510 topi) sulla memoria di riferimento spaziale (ad esempio, 1,5,7,8). Figura 3 è il risultato rappresentativo segnalato nel nostro studio che esamina l&#39;effetto di insorgenza nell&#39;età adulta espressione P301L tau sull&#39;apprendimento e la memoria 8, utilizzando il test Ambiente A. Per valutare le capacità motorie e visive, i topi son...

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.

Morris water maze Test: Ottimizzazione per ceppo di topi e Ambiente di prova

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

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21.3K Views.  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. 

Video: 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.

Acque poco profonde (Paddling) Varianti di test labirinto d&#39;acqua nei topi

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 ...

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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.

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.

Barnes strategie di sperimentazione Maze con piccole e grandi modelli di roditori

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.

The Double-H labirinto: una prova comportamentale robusto per l&#39;apprendimento e la memoria nei roditori

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.

Un protocollo per Mice Housing in un ambiente arricchito

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.

Il tapis roulant fatica di prova: un test semplice, high-throughput di stanchezza simile comportamento per il 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 ...

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.

Valutare l&#39;alterazione della memoria spaziale in un modello di topi di lesioni traumatiche del cervello usando un labirinto radiale

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.

Sperimentazione animale ansia in ratti: effetti di sporgenze braccio aperto e chiuso braccio parete trasparenza 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 ...

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.

Test per metacognitivo risponde utilizzando un odore-based ritardato Test Match a campione in ratti

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.

Attiva e passiva docilità separatamente nei topi di misura

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 ...