Name: the use of the puzzle box as a means of assessing the efficacy of environmental enrichment
Uploaded: 2014-12-29T14:00:00.000+00:00
Duration: 6 min 50 s
Description: Watch this Scientific Journal Video about The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment at JoVE.com

The authors have no acknowledgements.

Dichiarazione etica: Tutte le procedure sono state approvate dal comitato della University of Sydney Etica Animale ed adeguato alle Sanitario Nazionale e medicina Research Council di linee guida in Australia. Le procedure sono state effettuate su topi C57 / BL6J che sono stati allevati presso l&#39;Università di Sydney Bosch roditore strumento. Tutti i topi sono stati alloggiati in un unico locale sufficientemente ventilato in 21 ° C di temperatura ambiente in un ciclo luce-buio 12 ore con le luci alle 0600 ore in gabbie ventilazione individuale con ad libitum l&#39;accesso al cibo secco e acqua. Femmine tardo-gravidanza sono stati assegnati in modo casuale a condizioni di alloggio standard o arricchito l&#39;ambiente. 1. Housing (livelli di arricchimento): <ol><li> Ottenere 4 tarda gravidanza adulti topi femmina. Casualmente assegna 2 per la condizione standard e porre ciascuno di essi in una gabbia mouse standard pulito (ingombro 391 x 199 x 160 mm), contenente un mouse igloo rosso. Per la condizione arricchito, posizionare il remavorazio 2 topi in una singola gabbia topo-sized clean (ingombro 462 x 403 x 404 mm). </li><li> Nella gabbia di arricchimento, posizionare una varietà di oggetti progettati per aumentare la stimolazione sensoriale e motoria (ad esempio ruote corsa, stimoli visivi, batuffoli di cotone profumate, velcro). </li><li> Ogni 2 o 3 giorni si muovono questi oggetti circa all&#39;interno della gabbia; aggiornare qualsiasi che sono stati distrutti. </li><li> Dopo lo svezzamento a 21 giorni dopo la nascita, gli animali di sesso e il luogo in alloggi separati maschio-femmina in linea con le condizioni ambientali che sono state sollevate. Per la condizione arricchito in modo che ci sono tra i 3 ei 10 topi per gabbia con 2 e 5 topi per lo standard. Iniziare i test comportamentali una volta raggiunta l&#39;età adulta animali (12-14 settimane di età). </li></ol> 2. La costruzione del puzzle Box <ol><li> Ottenere 6 parti di acrilico bianco (o altro materiale non poroso): uno 750 x 280 mm, due 280 x 250 mm, due 750 x 250 mm, ed uno 150 x 280 mm (vedi figura 1). </li><li> Ottenere un pezzo di acrilico nero 280 x 250 mm, con una apertura quadrata di 40 x 40 mm tagliato in un lato di questo pezzo (vedi Figura 1). </li><li> Assemblare il puzzle Box come segue: usare il pezzo mm 750 x 280 come il fondo della scatola, utilizzare 280 x 250 mm pezzi come le estremità della scatola, ed i pezzi da 750 x 250 mm come lati della scatola. </li><li> Misurare 150 millimetri nella casella da un&#39;estremità, e posizionare il pezzo nero di acrilico attraverso la scatola in modo che si divide in due scomparti (uno grande, uno piccolo) con il filo apertura con il fondo della scatola. </li><li> Prendete il pezzo di mm acrilico bianco 150 x 280 e posizionarlo in cima al vano più piccolo della scatola assicurandosi che copre l&#39;area completamente, fornendo una camera oscura &quot;goal-box&quot;. Applicare questo pezzo di acrilico al corpo scatola principale cerniere, o lasciare libero di essere completamente rimosso durante la prova comportamentale. </li><li> Prendere 3 pezzi di acrilico (tre 4 x 120 mm) e unisciti a fare una &quot;u-shapchannel ed &quot;. </li></ol><img alt="Figura 1" fo:content-width="5in" src="/files/ftp_upload/52225/52225fig1highres.jpg" width="500" /> Figura 1: Schema del compito Puzzle Box. Il Puzzle Box è una scatola acrilica costituito da uno spazio aperto-campo (600 x 280 mm) e una zona riparata goal-box (150 x 280 mm), che misura 750 x 280 mm di tutti. Una apertura 40 x 40 mm all&#39;interno della partizione (grigio) che separa le due aree permette animali di accedere alla zona obiettivo-scatola coperta dal campo aperto. Questa apertura è bloccata con ostacoli sempre più difficili da rimuovere come test progredisce. Gli animali sono sottoposti ad un protocollo di cinque giorni, che consiste di quattro condizioni ostruzione con tre prove per ogni condizione. 3. Esecuzione della Task Puzzle Box <ol><li> Pulire accuratamente la scatola di puzzle con il 70% di alcol. Ripetere questo passaggio tra ogni testati su animali. </li><li> Posizionare un pulito il mouse igloo rosso nel ar obiettivo-boxEA del Puzzle Box, e sostituire il coperchio sul gol-box. </li><li> Se vi è una condizione di ostruzione in fase di test, posizionare l&#39;ostruzione all&#39;interno della soglia della meta-box (vedi figura 2). </li><li> Posizionare il mouse in fase di test nella sezione in campo aperto del Puzzle Box, orientato verso la meta-box, e alla più lontana dalla meta-box. </li><li> Registrare il tempo impiegato per tutte e quattro le zampe dell&#39;animale per entrare nella sezione obiettivo-box del Puzzle Box. </li><li> Se un animale non entra in porta-box, interrompere il processo una volta raggiunto il limite di tempo (vedi tabella 1). </li><li> Una volta che una prova è terminato, rimuovere l&#39;animale dalla Puzzle Box e metterlo in una gabbia un&#39;azienda distinta fino all&#39;inizio della prova successiva. Mantenere un gap 60 a 180 sec tra processi per ciascun animale. </li><li> Per ciascun animale, effettuare tre prove al giorno per cinque giorni consecutivi di test, con quattro condizioni ostruzione e tre prove di ciascuna condizione. Il terzo triAl di una data condizione ostruzione deve sempre somministrato su un giorno successivo (vedi Tabella 1). </li></ol><img alt="Tabella 1" fo:content-width="5in" src="/files/ftp_upload/52225/52225table1.jpg" width="500" /> Tabella 1: Schema del compito Puzzle Box. Il compito Puzzle Box viene eseguita per cinque giorni, e consiste di quattro condizioni ostruzione. Ci sono tre prove su ciascuno dei primi quattro giorni, e uno il quinto giorno. Ogni condizione di ostruzione ha tre prove; le prime due in un giorno, e il terzo giorno immediatamente successivo. La prima prova di una condizione di ostruzione mira a testare native capacità di risolvere problemi, il secondo processo esamina acquisizione compito e rinforzo, e la terza prova è usato come un test per la conservazione della soluzione e di richiamo. <img alt="Figura 2" fo:content-width="6in" src="/files/ftp_upload/52225/52225fig2highres.jpg" width="600" /> Figura 2: ostruirecondizioni di ioni all&#39;interno del compito Puzzle Box. Diagrammi di dell&#39;arena Puzzle Box e le condizioni di ostruzione utilizzati in questo studio. (A) Condizione 0 (C0), senza ostruzioni presenti all&#39;interno della porta tra il campo aperto e aree goal-box. (B) Condizione 1 (C1 ), con un canale presente &quot;U&quot; all&#39;interno della porta tra il campo aperto e aree obiettivo-box. (C) Condizione 2 (C2), in cui il canale è riempito con lettiera pulita. (D) Condizione 3 (C3 ), con un &quot;plug tissue&quot; presente nella porta tra il campo aperto e aree obiettivo-box. (E) Condizione 4 (C4) con un &quot;plug foam&quot; presente nella porta tra il campo aperto e meta-box aree. Dimensioni dell&#39;arena sono secondo elencato in Metodi e Figura 1. 4. Interpretazione dei dati <ol><li> Rappresentare i dati sia come tempo necessario per completare il processo (comprese le prove nulli in cui gli animali non è stata completata l&#39;operazione entro il termine previsto) o come il numero di prove nulli. </li><li> Utilizzare una misure ripetute ANOVA per valutare l&#39;effetto della condizione abitativa, all&#39;andamento nel Puzzle Box, con il tipo di ostruzione / condizioni (C) e il numero di task (T) entro soggetti fattori e il livello di arricchimento (standard contro arricchito) tra i soggetti-factor . </li></ol>

The authors declare they have no competing financial interests.

I dati presentati dimostrano che il Puzzle Box può essere utilizzato in modo efficace per valutare l&#39;impatto di EE. Topi allevati in ambienti arricchiti sempre preso molto meno tempo per risolvere i puzzle di ostruzione all&#39;interno di questa analisi comportamentale che ha animali allevati all&#39;interno di condizioni standard di laboratorio. Inoltre, questa differenza era più importante nella prima prova per tre delle quattro condizioni testate, suggerendo EE ha una maggiore influenza sulla native capacità d...

L&#39;arricchimento ambientale (EE) può essere definita come un ambiente che forniscono gli animali con maggiori opportunità di interazione sociale, attività motoria, e una maggiore stimolazione sensoriale del solito vissuto in un environment.EE standard di laboratorio ha dimostrato di influire in modo coerente il comportamento degli animali, determinando modifiche come la riduzione dello stress e l&#39;ansia di attività legate 8-10, il miglioramento delle prestazioni in compiti di apprendimento e memoria 8,11, insorgenza precoce di coordinazione motoria e l&#39;attività esplorativa 11, cambiamenti di cure materne 8 nonché resistenza alle sostanze stupefacenti 12- 15. Inoltre, EE è stato rivelato per migliorare gli effetti delle malattie neurodegenerative, ritardando l&#39;insorgenza e diminuire la gravità dei sintomi in modelli animali di Huntington di 1-4,16, Parkinson 17 e malattia di Alzheimer 18. Questi cambiamenti COrrelazione con le alterazioni anatomiche e molecolari EE è noto per indurre in tutto il cervello. Animali allevati in ambienti arricchiti dalle prime fasi di sviluppo mostrano una miriade di cambiamenti neurali, tra cui un aumento di peso del cervello e lo spessore corticale, dendritica ramificazione 9,2-22 e la densità sinaptica 23. EE può alterare sia il livello e la tempistica di espressione del fattore di crescita 9,24-30, che ha dimostrato di contribuire allo sviluppo accelerato sensoriale 25,26,28,29, mnemonico 30, nonché circuiti motori 31,32. Il lavoro precedente ha rivelato a risultati contraddittori momenti in cui si esamini l&#39;impatto di EE, senza tener conto dei diversi tipi di animali e ambienti utilizzati all&#39;interno dei singoli studi 9,24,27,30. Attualmente, non esiste compito comportamentale coerente e semplice che può essere utilizzato per misurare l&#39;efficacia di diversi paradigmi EE in ceppi diversi e specIES di animali. Il compito Puzzle Box è stato concepito come un semplice test per determinare problema nativa di un animale solving 7. Gli animali posti in zona aperta sono tenuti a rimuovere ostacolare materiali situati all&#39;interno di una piccola apertura per poter accedere a una coperta regione / rifugio. Ciascun soggetto è dato tre prove con lo stesso ostruzione per valutare tre diversi attributi cognitive. La prima prova si ottiene un indicazione di base di capacità di problem solving intrinseca o nativa. La seconda prova, eseguire lo stesso giorno, dà qualche indicazione della capacità dell&#39;animale di migliorare e rafforzare le strategie per rimuovere l&#39;ostruzione specifica in tal modo. La terza prova, condotta il giorno seguente, permette di comprendere meglio la capacità del soggetto di trattenere e richiamare la soluzione imparato al compito. La motivazione per risolvere questi &quot;enigmi ostruzione&quot; di animali può essere variata, potenzialmenteevocando un innato desiderio di evitare campi aperti e cercare riparo, così come un&#39;unità intrinseca di esplorare l&#39;ambiente circostante 6,7. La moltitudine di potenziali conducenti comportamentali alla base del desiderio di risolvere il puzzle Box suggerisce che diverse aree del cervello sono coinvolte nella mediazione prestazioni compito. Il lavoro precedente ha mostrato che in modelli murini di schizofrenia, corteccia prefrontale e l&#39;ippocampo sono coinvolti nell&#39;acquisizione di questo compito 5. Uno studio della lesione nei ratti ha rivelato anche un gran numero di regioni cerebrali coinvolte nella prestazione Puzzle Box, tra cui vari nuclei del talamo, l&#39;ipotalamo, il cervelletto, e le strutture limbiche. Insieme, questi risultati indicano che impegnarsi in questo problem solving compito comporta una serie di strutture neurali associate alla funzione cognitiva. Il Puzzle Box è stato utilizzato con successo per valutare la capacità di problem solving di topi, così come deficit cognitivi esposto da mmodelli di urina di schizofrenia 5-7. Prestazioni del compito ha dimostrato di essere altamente coerente, e correlare bene con risultati di altri test cognitivi comportamentali 6. L&#39;obiettivo di questo lavoro è stato quindi di adattare il compito Puzzle Box per diventare un mezzo semplice ed affidabile per determinare l&#39;efficacia di EE.

<table><tbody><tr><td>Black Acrylic Board</td><td></td><td></td><td>280 x 250 mm with a 40 x 40 mm &quot;door&quot; cut into one side</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>280 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>280 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>750 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>750 x 250 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td>150 x 280 mm</td></tr><tr><td>White Acrylic Board</td><td></td><td></td><td></td></tr><tr><td>Underpass</td><td></td><td></td><td>3 pieces of 40 x 120 mm plexiglass or acrylic</td></tr><tr><td colspan="4">Note: If unable to access acrylic board, plexiglass or similar non-porous material will suffice.</td></tr><tr><td>Webcam</td><td>Logitech</td><td>C210</td><td>Fix to roof with electrical tape. Alternatively, use a tripod.</td></tr><tr><td>VirtualDub v1.10.4</td><td>VirtualDub</td><td>N/A&amp;nbsp;</td><td>Software for recording behaviour videos. Input from webcam.</td></tr><tr><td>TopScan v 3.0</td><td>CleverSys Inc.</td><td>N/A&amp;nbsp;</td><td>Software for automated top-view tracking and analysis of mouse behaviour. Captured videos are analysed post-hoc.</td></tr></tbody></table>

the use of the puzzle box as a means of assessing the efficacy of environmental enrichment

Environmental enrichment can dramatically influence the development and function of neural circuits. Further, enrichment has been shown to successfully delay the onset of symptoms in models of Huntington&#8217;s disease 1-4, suggesting environmental factors can evoke a neuroprotective effect against the progressive, cellular level damage observed in neurodegenerative disorders. The ways in which an animal can be environmentally enriched, however, can vary considerably. Further, there is no straightforward manner in which the effects of environmental enrichment can be assessed: most methods require either fairly complicated behavioral paradigms and/or postmortem anatomical/physiological analyses. This protocol describes the use of a simple and inexpensive behavioral assay, the Puzzle Box 5-7 as a robust means of determining the efficacy of increased social, sensory and motor stimulation on mice compared to cohorts raised in standard laboratory conditions. This simple problem solving task takes advantage of a rodent&#8217;s innate desire to avoid open enclosures by seeking shelter. Cognitive ability is assessed by adding increasingly complex impediments to the shelter&#8217;s entrance. The time a given subject takes to successfully remove the obstructions and enter the shelter serves as the primary metric for task performance. This method could provide a reliable means of rapidly assessing the efficacy of different enrichment protocols on cognitive function, thus paving the way for systematically determining the role specific environmental factors play in delaying the onset of neurodevelopmental and neurodegenerative disease.

I risultati qui descritti sono un campione rappresentativo, con i dati provenienti dalle diverse coorti composte da diverse cucciolate. Tutti i test comportamentali è stato condotto tra il 0700 e 1100 ore, con ordine sperimentazione casuale di animali all&#39;interno di una coorte. Animali sollevate in un ambiente arricchito (n = 14, 7 femmine e 7 maschi) hanno significativamente meno tempo per risolvere i compiti ostruzione all&#39;interno della scatola Puzzle di quelle sollevate in un ambiente standard (n = 15, 7 fem...

Watch this Scientific Journal Video about The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment at JoVE.com

The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple &#8220;Puzzle Box&#8221; method for assessing an animal&#8217;s cognitive function, in order to reveal the effectiveness of environmental enrichment.

L&#39;uso del Puzzle Box come un mezzo per valutare l&#39;efficacia di arricchimento ambientale

Environmental enrichment can dramatically influence the development and function of neural circuits.  Further, enrichment has been shown to successfully ...

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Research

JoVE Journal

Behavior

11.6K Views.  University of Sydney. Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple “Puzzle Box” method for assessing an animal’s cognitive function, in order to reveal the effectiveness of environmental enrichment.

Video: The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

The Hole Consiglio Modified - Behavior, Cognition e l&#39;interazione sociale in topi e ratti di misura

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

Ricerca

Comportamento

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 ...

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.
Burrowing was first developed in Oxford13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.6



Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it8.



Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality5. 



A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

Burrowing, nesting, and hoarding are species-typical activities that mice readily perform in the laboratory. This article describes how they can be easily and cheaply assessed. These protocols are extremely sensitive to mouse strain, brain lesions and diseases. Moreover they constitute &#x201C;environmental enrichment&#x201D; for the mice, and embody the &#x201C;Refinement&#x201D; aspect of the &#x201C;3 Rs&#x201D;18.

Valutare scavatori, Costruzione nido, e Tesaurizzazione in topi

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

Neuroscienze

Novel Object Exploration as a Potential Assay for Higher Order Repetitive Behaviors in Mice

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals. RRBs are commonly split into lower-order and higher-order components, with lower order RRBs consisting of motor stereotypies and higher order RRBs consisting of perseverative and sequencing behaviors. Higher order RRBs are challenging to model in mice. Current assays for RRBs in mice focus primarily on the lower order components, making basic biomedical research into potential treatments or interventions for higher-order RRBs difficult. Here we describe a new assay, novel object exploration. This assay uses a basic open-field arena with four novel objects placed around the perimeter. The test mouse is allowed to freely explore the arena and the order in which the mouse investigates the novel objects is recorded. From these data, patterned sequences of exploration can be identified, as can the most preferred object for each mouse. The representative data shared here and past results using the novel object exploration assay illustrate that inbred mouse strains do demonstrate different behavior in this assay and that strains with elevated lower order RRBs also show elevated patterned behavior. As such, the novel object exploration assay appears to possess good face validity for higher order RRBs in humans and may be a valuable assay for future studies investigating novel therapeutics for ASD.

Higher order restricted, repetitive behaviors (RRBs) disrupt the lives of affected individuals. These behaviors are challenging to model in rodents, making basic biomedical research into potential treatments or interventions for RRBs difficult. Here we describe novel object exploration as a potential assay for higher order RRBs in mice.

Esplorazione oggetto romanzo come un test Potenziale di ordine superiore ripetitivi comportamenti nei topi

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals.  RRBs are ...

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous research determined a profound impact of gentle handling protocols on the well-being of laboratory mice. By introducing clicker training to the keeping of mice, not only do we promote the amicable treatment of mice, but we also enable them to experience cognitive enrichment. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcer, the "click" sound of a clicker, which serves as a time bridge between the strengthened behavior and an upcoming reward. The effective implementation of the clicker training protocol with a cohort of 12 BALB/c inbred mice of each sex proved to be uncomplicated. The mice learned rather quickly when challenged with tasks of the clicker training protocol, and almost all trained mice overcame the challenges they were given (100% of female mice and 83% of male mice). This study has identified that clicker training for mice strongly correlates with reduced fear in the mice during human-mice interactions, as shown by reduced anxiety-related behaviors (e.g., defecation, vocalization, and urination) and fewer depression-like behaviors (e.g., floating). By developing a reliable protocol that can be easily integrated into the daily routine of the keeping of laboratory mice, the lifetime experience of welfare in the mice can be improved substantially.

The development of new refinement strategies for laboratory mice is a challenging task that contributes towards fulfilling the 3R principle. This protocol introduces clicker training as a cognitive enrichment program for laboratory mice.

L&#39;introduzione di Clicker Training come un arricchimento conoscitivo per topi di laboratorio

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous ...

Analyzing Spatial Learning and Prosocial Behavior in Mice Using the Barnes Maze and Damsel-in-Distress Paradigms

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. The Barnes maze can also assess other mouse behaviors, such as general motivation to escape from the maze platform and exploratory behavior. The Barnes maze can measure whether a genetic mutation or environmental variable can impact the acquisition and retention of spatial memories, as well as provide information about the search strategy employed by the mice. Here we use the Barnes maze to detect a memory deficit in adult mice following a single developmental ethanol exposure event. The newly described Damsel-in-Distress paradigm exposes a male mouse to a female mouse trapped in a chamber in the open center field of the arena. It provides an opportunity for the mouse to socially respond to the trapped female and exhibit prosocial behavior. The Damsel-in-Distress paradigm can also be used to examine mouse behavior in a novel arena and measure locomotor activity. Both the Barnes Maze and the Damsel-in-Distress protocols require minimal financial investment and most aspects of the tests can be constructed from common lab supplies. These flexible and accessible tools can also be used to detect behavioral changes over the course of development.

This protocol measures spatial learning and memory using the Barnes maze. A novel Damsel-in-Distress paradigm is used to assess locomotor activity and prosocial behavior in mice.

Analisi apprendimento spaziale e comportamento prosociale nei topi utilizzando il labirinto di Barnes e paradigmi Damsel in Distress

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. ...

Assessment of Memory Function in Pilocarpine-induced Epileptic Mice

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal model of epilepsy, we generated pilocarpine-treated chronic epileptic mice. We present a protocol for three different behavioral tests using these epileptic mice: novel object location (NL), novel object recognition (NO), and pattern separation (PS) tests to evaluate learning and memory for places, objects, and contexts, respectively. We explain how to set the behavioral apparatus and provide experimental procedures for the NL, NO, and PS tests following an open field test that measures the animals&#8217; basal locomotor activities. We also describe the technical advantages of the NL, NO, and PS tests with respect to other behavioral tests for assessing memory function in epileptic mice. Finally, we discuss possible causes and solutions for epileptic mice failing to make 30 s of good contact with the objects during the familiarization sessions, which is a critical step for successful memory tests. Thus, this protocol provides detailed information about how to assess epilepsy-associated memory impairments using mice. The NL, NO, and PS tests are simple, efficient assays that are appropriate for the evaluation of different kinds of memory in epileptic mice.

This article presents experimental procedures for assessing memory impairments in pilocarpine-induced epileptic mice. This protocol can be used to study the pathophysiologic mechanisms of epilepsy-associated cognitive decline, which is one of the most common comorbidities in epilepsy.

Valutazione della funzione di memoria nei topi epilettici indotti da pilocarpina

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal ...

The Innovation Arena: A Method for Comparing Innovative Problem-Solving Across Groups

Problem-solving tasks are commonly used to investigate technical, innovative behavior but a comparison of this ability across a broad range of species is a challenging undertaking. Specific predispositions, such as the morphological toolkit of a species or exploration techniques, can substantially influence performance in such tasks, which makes direct comparisons difficult. The method presented here was developed to be more robust with regard to such species-specific differences: the Innovation Arena presents 20 different problem-solving tasks. All tasks are presented simultaneously. Subjects are confronted with the apparatus repeatedly, which allows a measurement of the emergence of innovations over time - an important next step for investigating how animals can adapt to changing environmental conditions through innovative behavior.
Each individual was tested with the apparatus until it ceased to discover solutions. After testing was concluded, we analyzed the video recordings and coded successful retrieval of rewards and multiple apparatus-directed behaviors. The latter were analyzed using a Principal Component Analysis and the resulting components were then included in a Generalized Linear Mixed Model together with session number and the group comparison of interest to predict the probability of success.
We used this approach in a first study to target the question of whether long-term captivity influences the problem-solving ability of a parrot species known for its innovative behavior: the Goffin&#180;s cockatoo. We found an effect in degree of motivation but no difference in the problem-solving ability between short- and long-term captive groups.

The Innovation Arena is a novel comparative method for studying technical innovation rate per time unit in animals. It is composed of 20 different problem-solving tasks, which are presented simultaneously. Innovations can be carried out freely and the setup is robust with regard to predispositions on an individual, population or species level.

L'arena dell'innovazione: un metodo per confrontare la risoluzione di problemi innovativi tra i gruppi

Problem-solving tasks are commonly used to investigate technical, innovative behavior but a comparison of this ability across a broad range of species is ...

Assessment of Mouse Judgment Bias through an Olfactory Digging Task

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This phenomenon has long been observed in humans, with individuals in positive states responding to ambiguity 'optimistically' and those in negative states instead showing 'pessimism'. Researchers aiming to assess animal affect have taken advantage of these differential responses, developing tasks to assess judgment bias as an indicator of affective state. These tasks are becoming increasingly popular across diverse species and fields of research. However, for laboratory mice, the most widely used vertebrates in research and a species heavily relied upon to model affective disorders, only one JB task has been successfully validated as sensitive to changes in affective state. Here, we provide a detailed description of this novel murine JB task, and evidence of its sensitivity to mouse affect. Though refinements are still necessary, assessment of mouse JB opens the door for answering both practical questions regarding mouse welfare, and fundamental questions about the impact of affective state in translational research.

This article provides a detailed description of a novel mouse judgment bias protocol. Evidence of this olfactory digging task's sensitivity to affective state is also demonstrated and its utility across diverse research fields is discussed.

Valutazione del pregiudizio del giudizio del topo attraverso un'attività di scavo olfattivo

Judgment biases (JB) are differences in the way that individuals in positive and negative affective/emotional states interpret ambiguous information. This ...

Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice

Long-lasting changes in the brain or &#8216;brain plasticity&#8217; underlie adaptive behavior and brain repair following disease or injury. Furthermore, interactions with our environment can induce brain plasticity. Increasingly, research is trying to identify which environments stimulate brain plasticity beneficial for treating brain and behavioral disorders. Two environmental manipulations are described which increase or decrease the number of tyrosine hydroxylase immunopositive (TH+, the rate-limiting enzyme in dopamine (DA) synthesis) neurons in the adult mouse midbrain. The first comprises pairing male and female mice together continuously for 1 week, which increases midbrain TH+ neurons by approximately 12% in males, but decreases midbrain TH+ neurons by approximately 12% in females. The second comprises housing mice continuously for 2 weeks in &#8216;enriched environments&#8217; (EE) containing running wheels, toys, ropes, nesting material, etc., which increases midbrain TH+ neurons by approximately 14% in males. Additionally, a protocol is described for concurrently infusing drugs directly into the midbrain during these environmental manipulations to help identify mechanisms underlying environmentally-induced brain plasticity. For example, EE-induction of more midbrain TH+ neurons is abolished by concurrent blockade of synaptic input onto midbrain neurons. Together, these data indicate that information about the environment is relayed via synaptic input to midbrain neurons to switch on or off expression of &#8216;DA&#8217; genes. Thus, appropriate environmental stimulation, or drug targeting of the underlying mechanisms, might be helpful for treating brain and behavioral disorders associated with imbalances in midbrain DA (e.g. Parkinson&#8217;s disease, attention deficit and hyperactivity disorder, schizophrenia, and drug addiction).

This protocol describes two different environmental manipulations and a concurrent brain infusion protocol to study environmentally-induced brain changes underlying adaptive behavior and brain repair in adult mice.

Modulazioni ambientali del numero di Mesencefalo dopamina neuroni in topi adulti

Long-lasting changes in the brain or &#8216;brain plasticity&#8217; underlie adaptive behavior and brain repair following disease or injury. Furthermore, ...

L'uso del Puzzle Box come un mezzo per valutare l'efficacia di arricchimento ambientale

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The Hole Consiglio Modified - Behavior, Cognition e l'interazione sociale in topi e ratti di misura