Questo lavoro è stato finanziato da sovvenzioni del Fondo nazionale svizzero (Grant 31003A-149315-1 per MES e di Grant IZK0Z3-150809 di AZ), per AZ il Demetriades Fondazione Heidi, al MES il Consiglio europeo della ricerca (&#39;Nogorise&#39;) e la Christopher e Dana Reeve Foundation (CDRF).

Tutti gli esperimenti sono stati eseguiti in conformità con le linee guida del veterinario del Cantone di Zurigo, Svizzera. 1. Manipolazione di animali e assuefazione <ol><li> Manipolazione di animali Nota: 5 giorni prima dell&#39;inizio dell&#39;esperimento, eseguire il passaggio 1.1.1 giornaliera. <ol><li> Per gli esperimenti comportamentali, abituare gli animali allo sperimentatore. Hanno quotidiana gestione sessioni della durata di 10-15 minuti per ogni animale. Pulire la scatola dopo la sessione di ogni animale. <ol><li> Inizialmente, mettere la mano dello sperimentatore in una gabbia che permette all&#39;animale di esplorare e sentire l&#39;odore di diventare familiarizzato con lo sperimentatore. </li><li> Successivamente, sollevare delicatamente l&#39;animale con la mano dello sperimentatore in modo sicuro afferrando il corpo del topo tra le zampe anteriori e posteriori che consentano una ulteriore familiarizzazione. </li></ol></li><li> Pesare ogni animale al giorno per ottenere un peso corporeo di base prima di privazione di cibo. </li></ol&gt; </li><li> Apparato assuefazione e familiarizzazione alimentare <ol><li> Pesare ogni animale al giorno per ottenere un peso corporeo di base prima di privazione di cibo. </li><li> Inizia cibo privando ratti 3 giorni prima l&#39;inizio del pre-allenamento su una dieta standard di laboratorio. Dare ratti 0,05 g di alimento per 1 g di peso corporeo al giorno (per esempio, un ratto peso 200 g, iniziare con 10 g di cibo). Assicurarsi peso corporeo di non diminuire di più del 10% al giorno monitorando peso corporeo al giorno. <ol><li> Se più animali vengono tenuti in una gabbia, i ratti dominanti possono mangiare più di quelli meno dominanti. Nel caso in cui il peso di un animale diminuisce, nutrire l&#39;animale separatamente invece di gruppo di alimentazione. Dare acqua ad libitum. </li></ol></li><li> Per conoscere il topo con l&#39;apparato di presa, collocare l&#39;animale nella scatola di formazione (Figura 1). Avere pellets zucchero immessi nella casella di formazione in prossimità dell&#39;apertura della fessura per conoscere l&#39;animale con i pellet cibo. Eseguire questo step 10-15 minuti al giorno per 3 giorni. </li></ol></li></ol> 2. Pre-allenamento e abilità di apprendimento Motor <ol><li> Pre-training <ol><li> Un giorno dopo familiarizzazione, posizionare l&#39;animale nella scatola formazione e posizionare il pellet strettamente per l&#39;apertura a fessura in modo che possa essere raggiunto dalla linguetta dell&#39;animale. Escludere gli animali che recuperano pellet con loro arti anteriori durante la pre-formazione Nota: In questa fase, il recupero pellet con la lingua è cruciale e solito metodo dell&#39;animale di scelta. Pellet devono essere in nessun caso colto con la zampa anteriore fino al primo giorno di apprendimento delle capacità motorie per consentire un adeguato monitoraggio del compito di raggiungere imparato. Recupero pellet con la zampa anteriore durante la pre-formazione è un criterio di esclusione e in molti casi non osservate. </li><li> Insegna il ratto o correre sul retro della gabbia e tornare alla apertura a fessura o passo indietro e girare attorno al proprio asse per ricevere il cibo successiva pellet conla lingua. Attendere che l&#39;animale per esplorare la gabbia, eseguire verso la parte posteriore e tornare alla apertura a fessura. Se l&#39;animale non esegue correttamente il compito, utilizzare una pinza a picchiettare delicatamente sul retro fine della gabbia e catturare l&#39;attenzione dell&#39;animale. Una volta che l&#39;animale è sul retro, toccare delicatamente nella parte anteriore della gabbia per guidare l&#39;animale per l&#39;apertura a fessura. Nota: Una volta che l&#39;animale raggiunge un valore standard (ad esempio, 50 recuperi pellet di successo con la lingua in meno di 15 minuti), l&#39;animale si qualifica per la fase di apprendimento delle capacità motorie. Il giorno 1 e 2 di pre-formazione, gli studenti possono già essere distinti da non discenti. Non gli studenti possono essere esclusi dallo studio in questa fase. Questo diminuisce la probabilità di avere un alto numero di non studenti durante la fase di apprendimento del motore (2.2). </li><li> Durante la pre-formazione, cibo privare i ratti su una dieta standard di laboratorio. Dare acqua ad libitum. Monitorare peso corporeo al giorno nel corso dello studio. FareNon usare lo stesso spazio per allenarsi ratti maschi e femmine. Garantire un ambiente tranquillo e privo di rumore per l&#39;animale. </li></ol></li><li> Determinazione del Preference Paw e Skill Learning Motor <ol><li> Durante la prima sessione di apprendimento delle capacità motorie, sostituire la diapositiva davanti alla finestra con un post. Posizionare il pellet zucchero circa 1,5 cm di distanza dalla finestra sul montante in modo che l&#39;animale non può raggiungere il pellet con la lingua ma solo recuperare da un forelimb preciso di raggiungere e afferrare il movimento. <ol><li> Per applicare il recupero pellet dalla zampa anteriore, utilizzare una pinza per portare delicatamente il pellet vicino alla bocca dell&#39;animale e ritirare il pellet mentre l&#39;animale tenta consumo con la lingua. Effettuare questa operazione ripetutamente fino a quando l&#39;animale si allunga la zampa anteriore e afferra un pellet. </li></ol></li><li> Posizionare il montante centrale per l&#39;apertura della finestra. Per determinare la zampa preferenza, osservare con attenzione le prime 10 prove in giornata di formazione 1. Più del 70% del REACtentativi hing (cioè 7 su 10) devono essere eseguiti con la stessa arti anteriori. Se ciò non viene raggiunto, proseguire con un altro ciclo di 10 prove fino al raggiungimento della soglia del 70%. </li><li> Dopo la determinazione della zampa preferenza, spostare la posta verso la zampa anteriore preferito e allineare centrale al confine con l&#39;apertura della finestra. Allineamento paw preferita significa il post viene spostato contrario alla rispettiva zampa per consentire un angolo ottimale per raggiungere (Figura 1B, C). </li><li> Classificare un processo, definito come un nuovo pellet presentato all&#39;animale, come successo (raggiungere, afferrare, recuperare e mangiare il pellet), goccia (raggiungere, afferrare e perdere pellet durante il recupero) o non (battere pellet il palo). Annota ogni prova nel foglio e analizzare i dati dopo l&#39;esperimento. </li><li> Effettuare una sessione giornaliera costituito da un numero definito di prove (ad esempio, 150) o un tempo massimo (ad esempio, 1 ora) per ciascun animale. </li><li> Indagare precisione e messa a puntodel movimento utilizzando prima analisi tentativo. Un primo tentativo è definita afferrando il precipitato in un unico movimento monolitico senza interruzioni, esitazione o ripetizione di singoli componenti del movimento. Osservare attentamente ogni presa dal topo. <ol><li> Se il ratto esita o si ritrae durante una portata o tenta diverse prove di cogliere correttamente la pallina, annotare il relativo processo come il successo, ma non è il primo tentativo. Se l&#39;animale afferra con successo il pellet in un&#39;unica portata monolitico, annotare il relativo processo come successo il primo tentativo in una colonna separata nel foglio. </li></ol></li><li> Durante l&#39;apprendimento delle capacità motorie, cibo privare i ratti su una dieta standard di laboratorio. Dare acqua ad libitum. Monitorare peso corporeo al giorno nel corso dello studio. </li></ol></li></ol>

<ol>
	<li>Fu, M., Yu, X., Lu, J., Zuo, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetitive+motor+learning+induces+coordinated+formation+of+clustered+dendritic+spines+in+vivo.">Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo.</a> Nature. 483, 92-95 (2012).</li><li>Fu, M., Zuo, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experience-dependent+structural+plasticity+in+the+cortex.">Experience-dependent structural plasticity in the cortex.</a> Trends in neurosciences. 34, 177-187 (2011).</li><li>Holtmaat, A., Svoboda, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experience-dependent+structural+synaptic+plasticity+in+the+mammalian+brain.">Experience-dependent structural synaptic plasticity in the mammalian brain.</a> Nature reviews. Neuroscience. 10, 647-658 (2009).</li><li>Xu, T., 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=Rapid+formation+and+selective+stabilization+of+synapses+for+enduring+motor+memories.">Rapid formation and selective stabilization of synapses for enduring motor memories.</a> Nature. 462, 915-919 (2009).</li><li>Yu, X., Zuo, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spine+plasticity+in+the+motor+cortex.">Spine plasticity in the motor cortex.</a> Current opinion in neurobiology. 21, 169-174 (2011).</li><li>Rioult-Pedotti, M. S., Friedman, D., Donoghue, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Learning-induced LTP in neocortex. Science. 290, 533-536 (2000).</li><li>Rioult-Pedotti, M. S., Friedman, D., Hess, G., Donoghue, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strengthening+of+horizontal+cortical+connections+following+skill+learning.">Strengthening of horizontal cortical connections following skill learning.</a> Nature neuroscience. 1, 230-234 (1998).</li><li>Rioult-Pedotti, M. S., Donoghue, J. P., Dunaevsky, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Plasticity+of+the+synaptic+modification+range.">Plasticity of the synaptic modification range.</a> Journal of neurophysiology. 98, 3688-3695 (2007).</li><li>Fritsch, B., 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=Direct+current+stimulation+promotes+BDNF-dependent+synaptic+plasticity:+potential+implications+for+motor+learning.">Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning.</a> Neuron. 66, 198-204 (2010).</li><li>Ghiani, C. A., Ying, Z., de Vellis, J., Gomez-Pinilla, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise+decreases+myelin-associated+glycoprotein+expression+in+the+spinal+cord+and+positively+modulates+neuronal+growth.">Exercise decreases myelin-associated glycoprotein expression in the spinal cord and positively modulates neuronal growth.</a> Glia. 55, 966-975 (2007).</li><li>Josephson, 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=Activity-induced+and+developmental+downregulation+of+the+Nogo+receptor.">Activity-induced and developmental downregulation of the Nogo receptor.</a> Cell and tissue research. 311, 333-342 (2003).</li><li>Karlen, 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=Nogo+receptor+1+regulates+formation+of+lasting+memories.">Nogo receptor 1 regulates formation of lasting memories.</a> Proceedings of the National Academy of Sciences of the United States of America. 106, 20476-20481 (2009).</li><li>Kleim, J. A., Lussnig, E., Schwarz, E. R., Comery, T. A., Greenough, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synaptogenesis+and+Fos+expression+in+the+motor+cortex+of+the+adult+rat+after+motor+skill+learning.">Synaptogenesis and Fos expression in the motor cortex of the adult rat after motor skill learning.</a> The Journal of neuroscience : the official journal of the Society for Neuroscience. 16, 4529-4535 (1996).</li><li>Mironova, Y. A., Giger, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Where+no+synapses+go:+gatekeepers+of+circuit+remodeling+and+synaptic+strength.">Where no synapses go: gatekeepers of circuit remodeling and synaptic strength.</a> Trends in neurosciences. 14, 7-23 (2013).</li><li>Park, H., Poo, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurotrophin+regulation+of+neural+circuit+development+and+function.">Neurotrophin regulation of neural circuit development and function.</a> Nature reviews. Neuroscience. 14, 7-23 (2013).</li><li>Zemmar, 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=Neutralization+of+Nogo-A+enhances+synaptic+plasticity+in+the+rodent+motor+cortex+and+improves+motor+learning+in+vivo.">Neutralization of Nogo-A enhances synaptic plasticity in the rodent motor cortex and improves motor learning in vivo.</a> The Journal of neuroscience : the official journal of the Society for Neuroscience. 34, 8685-8698 (2014).</li><li>Whishaw, I. Q., Pellis, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+structure+of+skilled+forelimb+reaching+in+the+rat:+a+proximally+driven+movement+with+a+single+distal+rotatory+component.">The structure of skilled forelimb reaching in the rat: a proximally driven movement with a single distal rotatory component.</a> Behavioural brain research. 41, 49-59 (1990).</li><li>Buitrago, M. M., Ringer, T., Schulz, J. B., Dichgans, J., Luft, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+motor+skill+and+instrumental+learning+time+scales+in+a+skilled+reaching+task+in+rat.">Characterization of motor skill and instrumental learning time scales in a skilled reaching task in rat.</a> Behavioural brain research. 155, 249-256 (2004).</li><li>Geurts, A. 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=Knockout+rats+via+embryo+microinjection+of+zinc-finger+nucleases.">Knockout rats via embryo microinjection of zinc-finger nucleases.</a> Science. 325, 433 (2009).</li><li>Tews, B., 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=Synthetic+microRNA-mediated+downregulation+of+Nogo-A+in+transgenic+rats+reveals+its+role+as+regulator+of+synaptic+plasticity+and+cognitive+function.">Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulator of synaptic plasticity and cognitive function.</a> Proceedings of the National Academy of Sciences of the United States of America. , (2013).</li><li>Li, D., 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=Heritable+gene+targeting+in+the+mouse+and+rat+using+a+CRISPR-Cas+system.">Heritable gene targeting in the mouse and rat using a CRISPR-Cas system.</a> Nature. 31, 681-683 (2013).</li></ol>

The authors have nothing to disclose

Il paradigma mostrato in questo studio è adattato da Buitrago et al 18 e differisce dal classico singolo pellet raggiungendo paradigma 17 principalmente in due aspetti.: In primo luogo, lo studio miglioramento entro sessione permette l&#39;analisi del compito imparato in un solo giorno, che può fornire un diverso livello di informazioni, come ricerca del componente di apprendimento veloce rispetto al componente di apprendimento lenta rappresentati dai valori ...

Controllo del movimento è una funzione fondamentale del sistema nervoso centrale (CNS). Motricità è il principale uscita misurabile della funzione CNS e la principale possibilità per gli individui di interagire con il mondo esterno. Comprendere i principi di funzionamento del motore e dei meccanismi che sono alla base l&#39;apprendimento di un compito motorio è attualmente una delle grandi sfide nel campo delle neuroscienze. Cambiamenti morfologici, fisiologici e molecolari sono stati trovati al momento dell&#39;acquisto di un nuovo compito motorio. Ad esempio, la forma e il numero di sinapsi cambiano in risposta alla formazione qualificata motore 1-5, e cambiamenti funzionali della macchina sinaptica sono stati osservati dopo apprendimento motorio. Risposte sinaptiche erano più elevati nei collegamenti della regione forelimb rappresenta della corteccia motoria addestrato rispetto all&#39;emisfero inesperto dello stesso animale o risposte da animali non allenati 6,7. Osservazioni elettrofisiologiche suggeriscono anche che il potenziamento a lungo termine (LTP) e lungadepressione-termine (LTD) come meccanismi si svolgono durante l&#39;apprendimento di una nuova abilità motoria, e che il raggio d&#39;azione sinaptica, che è definito tra i confini limitanti di LTP e LTD saturazione, viene modificato 8. Inoltre, è stato dimostrato che i marker di attività e plasticità che promuovono molecole come c-fos, GAP-43, o BDNF ma anche plasticità molecole inibitrici, come Nogo-A di visualizzazione ruoli normativi per l&#39;apprendimento correlati neuronali plasticità 9-16. Questi progressi verso una migliore comprensione dei meccanismi alla base dell&#39;apprendimento motorio potrebbe essere raggiunto solo con l&#39;uso di paradigmi comportamentali che permettono un controllo preciso della acquisizione di una nuova capacità motorie, ad esempio, abile zampa anteriore portata. Solo un compito comportamentale ben strutturata permette di monitorare e catturare i cambiamenti che si verificano correlative su apprendimento e l&#39;esecuzione dei rispettivi compiti. Qui mostriamo visivamente una versione modificata del forelimb qualificatisingolo-pellet compito di raggiungere nei ratti adattati da Buitrago et al. 17 Il paradigma presentato consente l&#39;analisi dell&#39;acquisizione movimento all&#39;interno di una sessione di allenamento al giorno (entro sessione) che rappresenta la componente di apprendimento veloce e acquisizione primaria così come l&#39;apprendimento motorio qualificato in diverse sessioni (tra-session) che rappresenta la componente di apprendimento lenta e manutenzione del compito imparato 18. È importante sottolineare che questo paradigma comportamentale aumenta il grado di difficoltà e la complessità del compito abilità motoria a causa di due caratteristiche: in primo luogo, i ratti sono addestrati a girare intorno al proprio asse dopo ogni comprensione e quindi di riallineare il proprio corpo prima del prossimo pellet portata e rinnovare l&#39;orientamento del corpo, impedendo l&#39;esecuzione costante movimento dalla stessa angolazione. In secondo luogo, pellets vengono recuperati da un palo verticale posto davanti alla gabbia. A causa del piccolo diametro del palo, pellet possono essere facilmente dato il via richiede una comprensione precisa per il recupero di successo e preventing semplice trazione del pellet verso l&#39;animale. Tale test comportamentali complesso permette una maggiore comprensione dei meccanismi alla base dell&#39;apprendimento motorio. Rispetto ai topi, ratti sono superiori nella loro esecuzione dei compiti comportamentali complessi e quindi più adatto per paradigmi complessi come presentato in questo studio. Considerando le crescenti possibilità genetici disponibili per i ratti 19,20, la combinazione di metodi di analisi comportamentale precisi e ben controllati con manipolazioni genetiche, l&#39;imaging e tecniche fisiologiche rappresenta una potente cassetta degli attrezzi per capire meglio le basi neurobiologiche di apprendimento motorio e della memoria.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>1</td>
			<td>Training Box</td>
			<td>Self Made</td>
			<td></td>
		</tr>
		<tr>
			<td>2</td>
			<td>Pedestal</td>
			<td>Self Made</td>
			<td></td>
		</tr>
		<tr>
			<td>3</td>
			<td>Sugar Pellets</td>
			<td colspan="2">45-mg dustless precision pellets, TSE Systems Intl. Group</td>
		</tr>
		<tr>
			<td>4</td>
			<td>Animals</td>
			<td>5-6 week old Sprague Dawley Male Rats</td>
			<td></td>
		</tr>
		<tr>
			<td>5</td>
			<td>Laptop</td>
			<td>Hewlett Packard</td>
			<td></td>
		</tr>
		<tr>
			<td>6</td>
			<td>Stop Watch</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>7</td>
			<td>Forceps</td>
			<td>Fine Science Tools (FST)</td>
			<td></td>
		</tr>
		<tr>
			<td>8</td>
			<td>Software</td>
			<td>Excel (Microsoft), GraphPad Prism (GraphPad)</td>
			<td></td>
		</tr>
		<tr>
			<td>9</td>
			<td>Weighing scale</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>10</td>
			<td>Counter</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

acquisition of a high-precision skilled forelimb reaching task in rats

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor learning and execution is of critical importance in order to understand the principles and processes that underlie motor function. Here we present a paradigm to study movement acquisition within a daily session of training (within-session) representing the fast learning component and primary acquisition as well as skilled motor learning over several training sessions (between-session) representing the slow learning component and consolidation of the learned task. This behavioral paradigm increases the degree of difficulty and complexity of the motor skill task due to two features: First, the animal realigns its body prior to each pellet retrieval forcing renewed orientation and preventing movement execution from the same angle. Second, pellets are grasped from a vertical post that matches the diameter of the pellet and is placed in front of the cage. This requires a precise grasp for successful pellet retrieval and thus prevents simple pulling of the pellet towards the animal. In combination with novel genetics, imaging and electrophysiological technologies, this behavioral method will aid to understand the morphological, anatomical and molecular underpinnings of motor learning and memory.

Acquisizione di abilità motoria di successo si ottiene solo attraverso la pratica costante. Nonostante un attento esame di tutti gli aspetti, alcuni ratti riescono a imparare il compito (Figura 2). Questi &quot;non discenti o mancanza di motivazione conseguente pochi o assenti tentativi di recupero pellet dall&#39;inizio dell&#39;esperimento o in generale perdono interesse nel raggiungere per il pellet che portano alla riuscita continuamente tentativi. Al contrario, alcuni animali mostrano un comportam...

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Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

A paradigm is presented to analyze the acquisition of a high-precision skilled forelimb reaching task in rats.

Acquisizione di un alta precisione specializzata arti anteriori Raggiungere Task in Rats

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor ...

acquisition-of-a-high-precision-skilled-forelimb-reaching-task-in-rats

Universidad de Cartagena UDEC

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JoVE Journal

Behavior

10.2K Views.  University of Zurich. A paradigm is presented to analyze the acquisition of a high-precision skilled forelimb reaching task in rats.

Video: Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

La Task Congruenza crossmodali come un mezzo per ottenere una misura comportamentale Obiettivo della mano di gomma Illusion Paradigma

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

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A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake.
The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.
Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e.&#160;lever presses do not result in heroin delivery).
The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

A procedure that allows a demonstration of robust augmentation of drug seeking in food-restricted rats is described. Following heroin self-administration training, rats go through an abstinence period, in a drug-free environment, during which they are mildly food restricted. Drug seeking is then tested in the drug-associated environment.

Una procedura per studiare l&#39;effetto della prolungata restrizione alimentare sulla Cerco eroina nei ratti in astinenza

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing.

This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR).&#160;FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

Misura di fronto-limbico Attività L&#39;utilizzo di un emotivo Oddball attività nei bambini con familiare ad alto rischio per la schizofrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with ...

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, modifications to the standard task, can be used to systematically tax the neural systems controlling either attention or impulse control. Importantly, these challenges have consistent effects on behavior across laboratories in intact animals and can reveal either enhancements or deficits in cognitive function that are not apparent when rats are only tested on the standard task. The variety of behavioral measures that are collected can be used to determine if other factors (i.e., sedation, motivation deficits, locomotor impairments) are contributing to changes in performance. The versatility of the 5CSRTT is further enhanced because it is amenable to combination with pharmacological, molecular, and genetic techniques.

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, which are modifications of the standard task, increase flexibility of the task and can be combined with other manipulations to more fully characterize behavior.

Il 5-Choice reazione Serial Attività temporizzata: un lavoro di Attenzione e Impulse controllo per roditori

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

Una Procedura di osservare Context-indotta Rinnovo pavloviano condizionata alcol-seeking comportamento in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

fMRI Validation of fNIRS Measurements During a Naturalistic Task

We present a method to compare brain activity recorded with near-infrared spectroscopy (fNIRS) in a dance video game task to that recorded in a reduced version of the task using fMRI (functional magnetic resonance imaging). Recently, it has been shown that fNIRS can accurately record functional brain activities equivalent to those concurrently recorded with functional magnetic resonance imaging for classic psychophysical tasks and simple finger tapping paradigms. However, an often quoted benefit of fNIRS is that the technique allows for studying neural mechanisms of complex, naturalistic behaviors that are not possible using the constrained environment of fMRI. Our goal was to extend the findings of previous studies that have shown high correlation between concurrently recorded fNIRS and fMRI signals to compare neural recordings obtained in fMRI procedures to those separately obtained in naturalistic fNIRS experiments. Specifically, we developed a modified version of the dance video game Dance Dance Revolution (DDR) to be compatible with both fMRI and fNIRS imaging procedures. In this methodology we explain the modifications to the software and hardware for compatibility with each technique as well as the scanning and calibration procedures used to obtain representative results. The results of the study show a task-related increase in oxyhemoglobin in both modalities and demonstrate that it is possible to replicate the findings of fMRI using fNIRS in a naturalistic task. This technique represents a methodology to compare fMRI imaging paradigms which utilize a reduced-world environment to fNIRS in closer approximation to naturalistic, full-body activities and behaviors. Further development of this technique may apply to neurodegenerative diseases, such as Parkinson&#8217;s disease, late states of dementia, or those with magnetic susceptibility which are contraindicated for fMRI scanning.

We present a method to compare functional brain activity recorded during a naturalistic task using fNIRS with activity recorded during fMRI.

fMRI Validazione di fNIRS misurazioni durante un compito Naturalistica

We present a method to compare brain activity recorded with near-infrared spectroscopy (fNIRS) in a dance video game task to that recorded in a reduced ...

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 ...

Bouncing Ball with a Uniformly Varying Velocity in a Metronome Synchronization Task

Sensorimotor synchronization (SMS), a fundamental human ability to coordinate movements with external rhythms, has long been thought to be modality specific. In the canonical metronome synchronization task that requires tapping a finger along with an isochronous sequence, a well-established finding is that synchronization is much more stable to an auditory sequence consisting of auditory tones than to a visual sequence consisting of visual flashes. However, recent studies have shown that periodically moving visual stimuli can substantially improve synchronization compared with visual flashes. In particular, synchronization of a visual bouncing ball that has a uniformly varying velocity was found to be not less stable than synchronization of auditory tones. Here, the current protocol describes the application of the bouncing ball with a uniformly varying velocity in a metronome synchronization task. The usage of the bouncing ball in sequences with different inter-onset intervals (IOI) is included. The representative results illustrate synchronization performance of the bouncing ball, as compared with the performances of auditory tones and visual flashes. Given its comparable synchronization performance to that of auditory tones, the bouncing ball is of particular importance for addressing the current research topic of whether modality-specific mechanisms underlay SMS.

The purpose of this protocol is to introduce the application of a bouncing ball with a uniformly varying velocity in a metronome synchronization task.

Palla che rimbalza con una velocità uniforme variabile in un'attività di sincronizzazione di metronomo

Sensorimotor synchronization (SMS), a fundamental human ability to coordinate movements with external rhythms, has long been thought to be modality ...

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

L'attività di supinazione manopola: Un metodo semi-automatico per la valutazione della funzione degli arti anteriori in ratti

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

Evaluating Skilled Prehension in Mice Using an Auto-Trainer

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that permits the mouse to reach out of its cage and retrieve food pellets. Minimal food restriction is employed to encourage the mice to perform the food retrieval from the slot. As the mice begin to associate coming to the slot for food, the pellets are manually pulled away to stimulate extension and pronation of their paw to grasp and retrieve the pellet through the frontal slot. When the mice begin to reach for the pellets as they arrive at the slot, the behavioral assay can be performed by measuring the rate at which they successfully grasp and retrieve the desired pellet. They are then introduced to an auto-trainer that automates both the process of providing food pellets for the mouse to grasp, and the recording of successful and failed reaching and grasping attempts. This allows for the collection of reaching data for multiple mice with minimal effort, to be used in experimental analysis as appropriate.

Method to assess the impact of training on motor skills is a useful tool. Unfortunately, most behavioral assessments can be labor intensive and/or expensive.We describe here a robotic method of assessing prehension (reach-to-grasp) skill in mice.

Valutazione della prensione qualificata nei topi utilizzando un auto-allenatore

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that ...

Acquisizione di un alta precisione specializzata arti anteriori Raggiungere Task in Rats

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