Questo lavoro è stato supportato dal Department of Veterans Affairs Rehab R&D Service Career Development Awards (CDA-1, RX002111; CDA-2; RX002928) a RSA e (CDA-2, RX002342) ad AJF e National Institutes of Health (NIH-NICHD F31 HD097918 a DACT e NIH-NIEHS T32 ES012870 a DACT) e NEI Core Grant P30EY006360.

Tutte le procedure sono state approvate dall'Atlanta Veterans Affairs Institutional Animal Care and Use Committee e conformi alla guida del National Institutes of Health per la cura e l'uso di animali da laboratorio (NIH Publications, 8a edizione, aggiornata nel 2011).
1. La risposta optomotoria (OMR)
<ol><li>Impostare l'apparato OMR (dettagli su apparecchi e software nella Tabella dei materiali)
	<ol>
<li>Scegli la piattaforma di dimensioni appropriate per il roditore: topo, ratto o ratto grande/alterato (Figura 1A).</li>
		<li>Aprire il software OMR, che dovrebbe aprirsi in una finestra con diverse schede di opzioni e un feed video in diretta all'interno dell'OMR / tamburo virtuale (Figura 1B). Ingrandire o rimpicciolire con la videocamera secondo necessità in modo che la piattaforma e l'ambiente circostante siano visibili.</li>
		<li>Notare le icone lungo il lato sinistro dell'immagine dal vivo (Figura 1C). Fai clic sull'icona dell'asterisco e sull'icona delle strisce rotanti in modo che sia l'asterisco verde che le strisce rotanti verdi scompaiano dal feed live.</li>
		<li>Fare clic sull'icona della bussola in modo che vengano visualizzati un cerchio verde e due linee perpendicolari. Allunga il cerchio verde in modo che si allinei perfettamente con il cerchio nero sulla piattaforma, il che garantirà che l'OMR sia perfettamente allineato.</li>
		<li>Fare clic sull'icona della bussola perché non è necessario vedere il cerchio durante il test. Fai clic sull'icona dell'asterisco verde e sull'icona delle strisce rotanti verdi per farle riapparire. Si noti che le strisce verdi ruotano nella stessa direzione delle strisce nel tamburo, consentendo al ricercatore di conoscere la direzione delle strisce.</li>
		<li>Fare clic sulla scheda Test . In Test, fai clic sulla scheda Psicofisica . In Soglia selezionare Frequenza per misurare la frequenza spaziale. NOTA: il software OMR utilizza un paradigma di scala per calcolare automaticamente la frequenza spaziale (SF). Il contrasto sarà mantenuto al 100%.</li>
		<li>In Test, fare clic sulla scheda Predefiniti . Selezionare le impostazioni predefinite per Mouse18 o Rat20.</li>
		<li>In Test, fare clic sulla scheda Blanking . Seleziona la casella Blank on Tracking , che metterà in pausa le strisce / spegnerà gli schermi del computer nel tamburo ogni volta che si fa clic con il pulsante destro del mouse.</li>
		<li>Fare clic sulla scheda Risultati , che è dove verranno visualizzati i risultati del test.</li>
	</ol></li>
	<li>Valutare la frequenza spaziale
	<ol>
<li>Posizionare il roditore sulla piattaforma circolare al centro della camera di realtà virtuale composta da quattro monitor di computer che mostrano griglie a onda sinusoidale verticale che circondano la camera ad una velocità di 12 ° / s (Figura 1D).</li>
		<li>Si noti che la videocamera posizionata nella parte superiore della camera sta proiettando il comportamento del roditore dal vivo sul monitor del computer.</li>
		<li>Cerca la presenza o l'assenza di azioni riflessive da parte della testa del roditore mentre le grate si muovono in senso orario o antiorario. Assicurati che le barre illustrate siano visibili nel programma, che mostreranno la direzione del movimento della griglia.<ol>
<li>Fai attenzione che la testa del roditore si muova nella stessa direzione delle grate. Aspetta che ci sia un inseguimento regolare, non esplosioni irregolari di movimento della testa, per contarlo come tracciamento.</li>
			<li>Fare clic su Sì o No a seconda dei casi. Si noti che SF inizierà con 0,042 cyc / deg e si regolerà con ogni sì e no per diventare più facile o più difficile (Figura 1E). Fare clic su Ripristina se il test deve essere ripristinato a causa di un clic accidentale o errato di sì e no.</li>
		</ol>
</li>
		<li>Mentre il roditore viene testato, assicurati di mantenere l'asterisco posizionato sopra la testa del roditore. NOTA: Questo ha due effetti: 1) Mantiene la frequenza spaziale corretta. Se l'asterisco è posizionato tra le spalle, ad esempio, la frequenza spaziale sarà più bassa e le barre saranno più facili da vedere, risultando in un punteggio falsamente alto. 2) Per i roditori con lievi movimenti della testa, l'asterisco rende più facile valutare se la testa si sta effettivamente muovendo.</li>
		<li>Fai attenzione che il sistema dica "Fatto" quando viene raggiunta la frequenza spaziale del roditore. Si noti che i pulsanti Sì e No non saranno più cliccabili.</li>
		<li>Fare clic sulla scheda Risultati , che visualizzerà la frequenza spaziale per l'occhio sinistro, l'occhio destro e gli occhi combinati. NOTA: a volte il software è impostato in modo tale che i risultati vengano capovolti, ovvero l'occhio destro viene segnalato come occhio sinistro e l'occhio sinistro viene segnalato come occhio destro. Questo è stato scoperto durante la valutazione dei roditori che avevano un solo occhio lesionato in un modello di glaucoma.</li>
	</ol></li>
	<li>Valutare la sensibilità al contrasto NOTA: il test di sensibilità al contrasto può essere eseguito immediatamente dopo la fase di misurazione della frequenza spaziale o da solo nello stesso giorno o in un giorno diverso se il roditore appare affaticato dopo il test della frequenza spaziale (seguire i passaggi 1-2.2 se si verifica solo la sensibilità al contrasto).<ol>
<li>Fare clic sulla scheda Test e quindi sulla scheda Psicofisica . In Soglia selezionare Contrasto (singolo) per misurare la sensibilità al contrasto.</li>
		<li>Utilizzando anche un paradigma a scala, avviare grigliate con costante SF al culmine della curva sensibilità di contrasto (CS). Per fare ciò, fare clic sulla scheda Stimolo e quindi sulla scheda Grate . Nella casella Frequenza spaziale digitare 0,064 per i ratti e 0,103 per i topi.</li>
		<li>Inizia il contrasto al 100% e cerca gli stessi movimenti riflessivi della testa visti durante i test di frequenza spaziale. Si noti che il contrasto diminuirà man mano che il test progredisce fino a quando il roditore non avrà più movimenti riflessi della testa in risposta allo stimolo (Figura 1E).</li>
		<li>Fai attenzione che il sistema dica "Fatto" e che i pulsanti Sì e No non siano più cliccabili una volta che il roditore non risponde più allo stimolo visivo e la soglia di sensibilità al contrasto è stata raggiunta. Fare clic sulla scheda Risultati , in cui verrà elencata la sensibilità al contrasto per l'occhio sinistro, l'occhio destro e gli occhi combinati.</li>
	</ol></li>
	<li>Eseguire analisi post-test
	<ol>
<li>Per gli studi sulla retinopatia diabetica, in cui ci si aspetta che entrambi gli occhi abbiano deficit simili, utilizzare il punteggio combinato (media degli occhi destro e sinistro) per l'analisi. Per i modelli che causano danni differenziali agli occhi (ad esempio, lesioni da esplosione o glaucoma), tenere separati i dati dell'occhio sinistro e destro.</li>
		<li>Per Frequenza spaziale, utilizzare i punteggi grezzi (i dati della scheda Risultati ) per l'analisi e calcolare la media di questi punteggi insieme per gruppo (ad esempio, diabetico, controllo, ecc.).</li>
		<li>Per Sensibilità di contrasto, utilizzare il valore grezzo per calcolare la sensibilità di contrasto riportata dal contrasto di Michelson da una precedente misurazione della luminanza dello schermo.</li>
	</ol></li>
</ol>2. Il labirinto a Y
<ol><li>
Preparare i roditori per i test
	<ol>
<li>Adattare i roditori alla stanza per 30 minuti prima del test. NOTA: Il ricercatore può rimanere nella stanza con le luci accese ma dovrebbe rimanere in silenzio durante questo periodo.</li>
		<li>Pulire il labirinto a Y con una soluzione igienizzante sicura per gli animali e pulire via tutte le soluzioni igienizzanti con carta assorbente. Assicurati che il labirinto sia asciutto.</li>
	</ol>
</li>
	<li>
Condurre il labirinto a Y
	<ol>
<li>Etichettare il braccio iniziale del labirinto a Y come B e gli altri 2 bracci come A e C (Figura 2A). Posiziona un roditore nel braccio più vicino al ricercatore (braccio B) vicino al centro del labirinto a Y. Una volta posizionato il roditore, avviare il timer (dettagli sul labirinto e sul timer nella Tabella dei materiali).<ol>
<li>Consenti a ciascun roditore di esplorare il labirinto a Y per 8 minuti. Prendi le registrazioni durante questo periodo e prendi nota di eventuali osservazioni. Siediti a diversi metri di distanza dal labirinto mantenendolo in vista ed evita di fare rumore.</li>
			<li>Registrare la posizione di partenza come A e ogni volta che il roditore entra in un nuovo braccio, registrare la nuova posizione del roditore (Figura 2B). Definire una voce come tutti e quattro gli arti del roditore che si trovano in una delle braccia.</li>
			<li>Fai attenzione ai roditori per nascondersi e rimanere fermi in un braccio del labirinto. Se il roditore rimane nello stesso punto per più di 60 s e non sembra mostrare un comportamento esplorativo, sposta il roditore verso il centro del labirinto a Y e continua la prova.</li>
		</ol>
</li>
		<li>Dopo ogni roditore, rimuovere eventuali feci e pulire il labirinto con una soluzione igienizzante.<ol>
<li>Assicurarsi che tutta la soluzione igienizzante sia spazzata via con asciugamani di carta e che il labirinto sia completamente asciutto prima di posizionare il prossimo roditore nel labirinto.</li>
		</ol>
</li>
	</ol>
</li>
	<li>
Calcola l'alternanza spontanea e il comportamento esplorativo
	<ol>
<li>Calcola il comportamento esplorativo come il numero totale di voci effettuate durante 8 min.</li>
		<li>Calcola la cognizione spaziale misurata dall'alternanza spontanea: il numero di alternanze riuscite/(il numero totale di voci - 2)<ol>
<li>Definire un'alternanza di successo mentre il roditore si sposta in tre posizioni diverse in sequenza (esempio: ABC, CAB, BCA, ecc.). Annotare ogni alternanza riuscita (Figura 2B).</li>
			<li>Se i movimenti sono stati registrati come ACABCABABCABC, ignorare le due posizioni iniziali di partenza nel calcolo dell'alternanza spontanea (in modo tale che ci siano 11 movimenti nel denominatore). Contare il numero di movimenti precisi (movimenti accurati = 8). Calcola la precisione percentuale come: 8/(13 - 2) = 72,7%.</li>
		</ol>
</li>
	</ol>
</li>
</ol>

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F., L&#246;wel, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vision+and+visual+plasticity+in+ageing+mice.">Vision and visual plasticity in ageing mice.</a> Restorative Neurology and Neuroscience. 30, 161-178 (2012).</li><li>Leinonen, H., Tanila, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vision+in+laboratory+rodents-tools+to+measure+it+and+implications+for+behavioral+research.">Vision in laboratory rodents-tools to measure it and implications for behavioral research.</a> Behavioral Brain Research. 352, 172-182 (2018).</li><li>Spielmann, M., Schr&#246;ger, E., Kotz, S. A., Pechmann, T., Bendixen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+a+staircase+procedure+for+the+objective+measurement+of+auditory+stream+integration+and+segregation+thresholds.">Using a staircase procedure for the objective measurement of auditory stream integration and segregation thresholds.</a> Frontiers in Psychology. 4, 534 (2013).</li><li>Shi, 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=Optimization+of+optomotor+response-based+visual+function+assessment+in+mice.">Optimization of optomotor response-based visual function assessment in mice.</a> Scientific Reports. 8 (1), 9708 (2018).</li><li>You, M., Yamane, T., Tomita, H., Sugano, E., Akashi, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+rat+head+gaze+determination+system+based+on+optomotor+responses.">A novel rat head gaze determination system based on optomotor responses.</a> PLoS One. 12 (4), 0176633 (2017).</li><li>Whyte, A. 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Gli autori non hanno nulla da rivelare.

L'OMR e il labirinto Y consentono la valutazione non invasiva della funzione visiva e dei deficit cognitivi nei roditori nel tempo. In questo protocollo, l'OMR e il labirinto Y hanno dimostrato di tracciare i deficit visivi e cognitivi nei modelli di diabete dei roditori.
Passaggi critici nel protocollo
L'OMR
Alcuni punti importanti da considerare quando si esegue l'OMR per valutare la funzione visiva sono i parametri di ...

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61806">Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats</a>. The author list was updated.
The author list was updated from:
Kaavya Gudapati*1,2, Anayesha Singh*1,3, Danielle Clarkson-Townsend1,4, Andrew J. Feola1,2, Rachael S. Allen1,2 
1Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, 
2Department of Biomedical Engineering, Georgia Institute of Technology, 
3Department of Neuroscience, Emory University, 
4Gangarosa Department of Environmental Health, Emory University 
* These authors contributed equally
to:
Kaavya Gudapati*1,2, Anayesha Singh*1,3, Danielle Clarkson-Townsend1,4, Stephen Q. Phillips1, Amber Douglass1, Andrew J. Feola1,2, Rachael S. Allen1,2 
1Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, 
2Department of Biomedical Engineering, Georgia Institute of Technology, 
3Department of Neuroscience, Emory University, 
4Gangarosa Department of Environmental Health, Emory University 
* These authors contributed equally

An erratum was issued for:&#160;<a href="https://www.jove.com/t/61806">Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats</a>. The author list was updated.

Erratum: Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

Oltre 463 milioni di persone vivono con il diabete, rendendolo una delle più grandi epidemie di malattie globali1. Una delle gravi complicazioni che derivano dal diabete è la retinopatia diabetica (DR), una delle principali cause di cecità per gli adulti americani in età lavorativa2. Nei prossimi 30 anni, si prevede che la percentuale della popolazione a rischio di DR raddoppierà, quindi è fondamentale trovare nuovi modi di diagnosticare la DR nelle sue fasi iniziali per prevenire e mitigare lo sviluppo di DR3. La DR è stata convenzionalmente ritenuta una malattia vascolare4,5,6. Tuttavia, ora con evidenza di disfunzione neuronale e apoptosi nella retina che precede la patologia vascolare, la DR è definita per avere componenti neuronali e vascolari4,5,6,7,8,9. Un modo per diagnosticare la DR sarebbe quello di esaminare le anomalie neurali nella retina, un tessuto che può essere più vulnerabile allo stress ossidativo e allo sforzo metabolico da diabete rispetto ad altri tessuti neurali10.
I declini della funzione cognitiva e motoria si verificano anche con il diabete e sono spesso correlati con i cambiamenti della retina. Gli individui più anziani con diabete di tipo II ritraggono prestazioni cognitive di base peggiori e mostrano un declino cognitivo più esacerbato rispetto ai partecipanti al controllo11. Inoltre, la retina è stata stabilita come un'estensione del sistema nervoso centrale e le patologie possono manifestarsi nella retina12. Clinicamente, la relazione tra retina e cervello è stata studiata nel contesto dell'Alzheimer e di altre malattie, ma non è comunemente esplorata con il diabete12,13,14,15,16. I cambiamenti nel cervello e nella retina durante la progressione del diabete possono essere esplorati utilizzando modelli animali, tra cui il ratto STZ (un modello di diabete di tipo I in cui la tossina, streptozotocina o STZ, viene utilizzata per danneggiare le cellule beta pancreatiche) e il ratto Goto-Kakizaki (un modello poligenico di diabete di tipo II in cui gli animali sviluppano iperglicemia spontaneamente a circa 3 settimane di età). In questo protocollo, viene fornita una descrizione per il labirinto Y e la risposta optomotoria per valutare i cambiamenti cognitivi e visivi nei roditori diabetici, rispettivamente. La risposta optomotoria (OMR) valuta la frequenza spaziale (simile all'acuità visiva) e la sensibilità al contrasto monitorando i movimenti caratteristici di tracciamento riflessivo della testa per misurare le soglie visive per ciascun occhio17. La frequenza spaziale si riferisce allo spessore o alla finezza delle barre e la sensibilità al contrasto si riferisce alla quantità di contrasto tra le barre e lo sfondo (Figura 1E). Nel frattempo, il labirinto a Y testa la memoria spaziale a breve termine e la funzione esplorativa, osservata attraverso alternanze spontanee e ingressi attraverso i bracci del labirinto.
Entrambi i test possono essere eseguiti in animali svegli e non anestetizzati e hanno il vantaggio di capitalizzare sulle risposte innate degli animali, il che significa che non richiedono addestramento. Entrambi sono relativamente sensibili, in quanto possono essere utilizzati per rilevare i deficit nelle prime fasi della progressione del diabete nei roditori e affidabili, in quanto producono risultati correlati ad altri test visivi, retinici o comportamentali. Inoltre, l'utilizzo dell'OMR e del labirinto Y in combinazione con test come l'elettroretinogramma e le scansioni di tomografia a coerenza ottica può fornire informazioni su quando i cambiamenti retinici, strutturali e cognitivi si sviluppano l'uno rispetto all'altro nei modelli di malattia. Queste indagini potrebbero essere utili per identificare le degenerazioni neurali che si verificano a causa del diabete. In definitiva, questo potrebbe portare a nuovi metodi diagnostici che identificano efficacemente la DR nelle prime fasi della progressione.
I sistemi OMR e Y-maze utilizzati per sviluppare questo protocollo sono descritti nella Tabella dei materiali. Precedenti ricerche sull'OMR, di Prusky et al.18, e sul labirinto Y, di Maurice et al.19, sono state utilizzate come punto di partenza per sviluppare questo protocollo.

<table>
	<tbody>
		<tr>
			<td>OptoMotry HD</td>
			<td>CerebralMechanics Inc.</td>
			<td></td>
			<td>OMR apparatus &#38; software</td>
		</tr>
		<tr>
			<td>Timer</td>
			<td>Thomas Scientific</td>
			<td>810029AR</td>
			<td></td>
		</tr>
		<tr>
			<td>Y-Maze apparatus</td>
			<td>San Diego Instruments</td>
			<td>7001-043</td>
			<td>Available specifically for rats</td>
		</tr>
	</tbody>
</table>

behavioral assessment of visual function via optomotor response and cognitive function via y-maze in diabetic rats

La risposta optomotoria e il labirinto a Y sono test comportamentali utili per valutare rispettivamente la funzione visiva e cognitiva. La risposta optomotoria è uno strumento prezioso per monitorare i cambiamenti nelle soglie di frequenza spaziale (SF) e sensibilità al contrasto (CS) nel tempo in una serie di modelli di malattia retinica, tra cui la retinopatia diabetica. Allo stesso modo, il labirinto Y può essere utilizzato per monitorare la cognizione spaziale (misurata dall'alternanza spontanea) e il comportamento esplorativo (misurato da un certo numero di voci) in un certo numero di modelli di malattia che colpiscono il sistema nervoso centrale. I vantaggi della risposta optomotoria e del labirinto a Y includono la sensibilità, la velocità dei test, l'uso di risposte innate (non è necessario l'allenamento) e la capacità di essere eseguita su animali svegli (non anestetizzati). Qui, i protocolli sono descritti sia per la risposta optomotoria che per il labirinto a Y ed esempi del loro uso mostrati in modelli di diabete di tipo I e di tipo II. I metodi includono la preparazione di roditori e attrezzature, le prestazioni della risposta optomotoria e del labirinto a Y e l'analisi dei dati post-test.

L'OMR è considerato di successo se le soglie di frequenza spaziale e sensibilità al contrasto possono essere ottenute da un roditore. Qui, l'uso dell'OMR per valutare la frequenza spaziale è illustrato nei ratti brown-norvegia e long-evans di controllo naïve, sia giovani (3-6 mesi) che invecchiati (9-12 mesi). I ratti brown-norvegesi mostrano tipicamente una frequenza spaziale di base più elevata rispetto ai ratti Long-Evans. Inoltre, è stato osservato un effetto di invecchiamento sulla frequenza spaziale nei ratti...

Watch this Scientific Journal Video about Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats at JoVE.com

Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

La degenerazione neurale sia negli occhi che nel cervello a causa del diabete può essere osservata attraverso test comportamentali effettuati sui roditori. Il labirinto Y, una misura della cognizione spaziale, e la risposta optomotoria, una misura della funzione visiva, forniscono entrambi informazioni su potenziali diagnosi e trattamenti.

Valutazione comportamentale della funzione visiva tramite risposta optomotoria e funzione cognitiva tramite Y-Maze nei ratti diabetici

The optomotor response and the Y-maze are behavioral tests useful for assessing visual and cognitive function, respectively. The optomotor response is a ...

behavioral-assessment-visual-function-via-optomotor-response

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5.4K Views.  Atlanta VA Medical Center. La degenerazione neurale sia negli occhi che nel cervello a causa del diabete può essere osservata attraverso test comportamentali effettuati sui roditori. Il labirinto Y, una misura della cognizione spaziale, e la risposta optomotoria, una misura della funzione visiva, forniscono entrambi informazioni su potenziali diagnosi e trattamenti.

Video: Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

Assessment of Sensorimotor Function in Mouse Models of Parkinson&#039;s Disease

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

Valutazione della Sensorimotor funzione in modelli murini di malattia di Parkinson

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

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Comportamento

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 ...

Irrelevant Stimuli and Action Control: Analyzing the Influence of Ignored Stimuli via the Distractor-Response Binding Paradigm

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are frequently used in the research on human action control. One important question in these settings is how distractor stimuli, competing with the target stimulus for a response, influence actions. The distractor-response binding paradigm can be used to investigate this influence. It is particular useful to separately analyze response retrieval and distractor inhibition effects. Computer-based experiments are used to collect the data (reaction times and error rates). In a number of sequentially presented pairs of stimulus arrays (prime-probe design), participants respond to targets while ignoring distractor stimuli. Importantly, the factors response relation in the arrays of each pair (repetition vs. change) and distractor relation (repetition vs. change) are varied orthogonally. The repetition of the same distractor then has a different effect depending on response relation (repetition vs. change) between arrays. This result pattern can be explained by response retrieval due to distractor repetition. In addition, distractor inhibition effects are indicated by a general advantage due to distractor repetition. The described paradigm has proven useful to determine relevant parameters for response retrieval effects on human action.

The distractor-response binding paradigm is described. It can be used to shed light on the influence irrelevant stimuli, competing with targets for a response, can have on human action. Both response retrieval effects and distractor inhibition effects can be analyzed within the paradigm.

Stimoli irrilevanti e Azione di controllo: Analizzare l&#39;influenza di stimoli Ignorato tramite il distrattore-Response Binding Paradigm

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are ...

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 ...

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 ...

Simultaneous Recordings of Cortical Local Field Potentials and Electrocorticograms in Response to Nociceptive Laser Stimuli from Freely Moving Rats

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.e., electrocorticogram [ECoG] and scalp electroencephalogram [scalp EEG]) and inside the brain (i.e., local field potential [LFP]). To address this issue, we present here an animal protocol using freely moving rats. This protocol is composed of three main procedures: (1) animal preparation and surgical procedures, (2) a simultaneous recording of ECoG and LFP in response to nociceptive laser stimuli, and (3) data analysis and feature extraction. Specifically, with the help of a 3D-printed protective shell, both ECoG and LFP electrodes implanted on the rat&#39;s skull were securely held together. During data collection, laser pulses were delivered on the rat&#39;s forepaws through gaps in the bottom of the chamber when the animal was in spontaneous stillness. Ongoing white noise was played to avoid the activation of the auditory system by the laser-generated ultrasounds. As a consequence, only nociceptive responses were selectively recorded. Using the standard analytical procedures (e.g., band-pass filtering, epoch extraction, and baseline correction) to extract stimulus-related brain responses, we obtained results showing that LEPs with a high signal-to-noise ratio were simultaneously recorded from ECoG and LFP electrodes. This methodology makes the simultaneous recording of ECoG and LFP activities possible, which provides a bridge of electrocortical signals at the mesoscopic and macroscopic levels, thereby facilitating the investigation of nociceptive information processing in the brain.

We developed a technique that simultaneously records both electrocorticography and local field potentials in response to nociceptive laser stimuli from freely moving rats. This technique helps establish a direct relationship of electrocortical signals at the mesoscopic and macroscopic levels, which facilitates the investigation of nociceptive information processing in the brain.

Registrazioni simultanee di potenziali di campo locale corticale ed Electrocorticograms in risposta a stimoli nocicettivi Laser da liberi di muoversi

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and ...

Supramaximal Intensity Hypoxic Exercise and Vascular Function Assessment in Mice

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by international guidelines for patients suffering from cardiovascular diseases, more specifically, lower extremity artery diseases, where the patients' walking capacity is considerably altered, affecting their quality of life. 
Traditionally, both low continuous exercise and interval training have been used. Recently, supramaximal training has also been shown to improve athletes' performances via vascular adaptations, amongst other mechanisms. The combination of this type of training with hypoxia could bring an additional and/or synergic effect, which could be of interest for certain pathologies. Here, we describe how to perform supramaximal intensity training sessions in hypoxia on healthy mice at 150% of their maximal speed, using a motorized treadmill and a hypoxic box. We also show how to dissect the mouse in order to retrieve organs of interest, particularly the pulmonary artery, the abdominal aorta, and the iliac artery. Finally, we show how to perform ex vivo vascular function assessment on the retrieved vessels, using isometric tension studies.

High-intensity training in hypoxia is a protocol that has been proven to induce vascular adaptations potentially beneficial in some patients and to improve athletes&#39; repeated sprint ability. Here, we test the feasibility of training mice using that protocol and identify those vascular adaptations using ex vivo vascular function assessment.

Sopramassimale intensità di esercizio Hypoxic e valutazione di funzione vascolare in topi

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by ...

Investigating the Deployment of Visual Attention Before Accurate and Averaging Saccades via Eye Tracking and Assessment of Visual Sensitivity

This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we recorded the eye position of human participants engaged in a saccade task via eye tracking and assessed visual orientation discrimination performance at various locations during saccade preparation. Importantly, instead of using a single saccade target paradigm for which the saccade endpoint typically coincides roughly with the target, this protocol comprised the presentation of two nearby saccade targets, leading to a distinct spatial dissociation between target locations and saccade endpoint on a substantial number of trials. The paradigm allowed us to compare presaccadic visual discrimination performance at the endpoint of accurate saccades (landing at one of the saccade targets) and of averaging saccades (landing at an intermediate location in between the two targets). We observed a selective enhancement of visual sensitivity at the endpoint of accurate saccades but not at the endpoint of averaging saccades. Rather, before the execution of averaging saccades, visual sensitivity was equally enhanced at both targets, suggesting that saccade averaging follows from unresolved attentional selection among the saccade targets. These results argue against a mandatory coupling between visual attention and saccade programming based on a direct measure of presaccadic visual sensitivity rather than saccadic reaction times, which have been used in other protocols to draw similar conclusions. While our protocol provides a useful framework to investigate the relationship between visual attention and saccadic eye movements at the behavioral level, it can also be combined with electrophysiological measures to extend insights at the neuronal level.

This experimental protocol combined eye tracking and the assessment of presaccadic visual sensitivity in a dual task paradigm, consisting of a free choice saccade task and a visual discrimination task, to investigate the deployment of visual spatial attention before both, accurate and averaging saccades.

Studiando la distribuzione dell'attenzione visiva prima di saccadi Accurate e media tramite Eye-Tracking e valutazione della sensibilità visiva

This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we ...

Integrating Visual Psychophysical Assays within a Y-Maze to Isolate the Role that Visual Features Play in Navigational Decisions

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired investigations into collective motion, specifically, their ability to integrate environmental and social information across ecological contexts. This demonstration illustrates techniques used for quantifying behavioral responses of fish, in this case, Golden Shiner (Notemigonus crysoleucas), to visual stimuli using computer visualization and digital image analysis. Recent advancements in computer visualization allow for empirical testing in the lab where visual features can be controlled and finely manipulated to isolate the mechanisms of social interactions. The purpose of this method is to isolate visual features that can influence the directional decisions of the individual, whether solitary or with groups. This protocol provides specifics on the physical Y-maze domain, recording equipment, settings and calibrations of the projector and animation, experimental steps and data analyses. These techniques demonstrate that computer animation can elicit biologically-meaningful responses. Moreover, the techniques are easily adaptable to test alternative hypotheses, domains, and species for a broad range of experimental applications. The use of virtual stimuli allows for the reduction and replacement of the number of live animals required, and consequently reduces laboratory overhead.
This demonstration tests the hypothesis that small relative differences in the movement speeds (2 body lengths per second) of virtual conspecifics will improve the speed and accuracy with which shiners follow the directional cues provided by the virtual silhouettes. Results show that shiners directional decisions are significantly affected by increases in the speed of the visual cues, even in the presence of background noise (67% image coherency). In the absence of any motion cues, subjects chose their directions at random. The relationship between decision speed and cue speed was variable and increases in cue speed had a modestly disproportionate influence on directional accuracy.

Here, we present a protocol to demonstrate a behavioral assay that quantifies how alternative visual features, such as motion cues, influence directional decisions in fish. Representative data are presented on the speed and accuracy where Golden Shiner (Notemigonus crysoleucas) follow virtual fish movements.

Integrazione di analisi psicofisiche visive all'interno di un Y-Maze per isolare il ruolo che le funzionalità visive svolgono nelle decisioni di navigazione

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired ...

Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson's Disease

As Parkinson&#8217;s disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard scores from paper and pencil symptom- measures traditionally used to track disease progression are too coarse (discrete) to capture the granularity of the clinical phenomena under consideration, in the face of tremendous symptom diversity. For this reason, sensors, wearables, and mobile devices are increasingly incorporated into PD research and routine care. These digital measures, while more precise, yield data that are less standardized and interpretable than traditional measures, and consequently, the two types of data remain largely siloed. Both of these issues present barriers to the broad clinical application of the field&#8217;s most precise assessment tools. This protocol addresses both problems. Using traditional tasks to measure cognition and motor control, we test the participant, while co-registering biophysical signals unobtrusively using wearables. We then integrate the scores from traditional paper-and-pencil methods with the digital data that we continuously register. We offer a new standardized data type and unifying statistical platform that enables the dynamic tracking of change in the person&#8217;s stochastic signatures under different conditions that probe different functional levels of neuromotor control, ranging from voluntary to autonomic. The protocol and standardized statistical framework offer dynamic digital biomarkers of physical and cognitive function in PD that correspond to validated clinical scales, while significantly improving their precision.&#160;

This protocol offers a digitization of portions of traditional clinical tasks commonly used to measure cognition and motor control in Parkinson&#8217;s disease. Clinical tasks are digitized while biophysical rhythms are co-registered from different functional levels of the nervous systems, ranging from voluntary, spontaneous, automatic to autonomic.

Biomarcatori digitali dinamici della funzione motoria e cognitiva nella malattia di Parkinson

As Parkinson&#8217;s disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard ...