Los autores agradecen la asistencia y asesoramiento técnico y logístico brindado por Rose Tobias, Younghee Ahn y David N. Ruskin. El trabajo aquí descrito fue financiado por la Fundación de Niños de Alberta el Hospital y el Instituto de Investigación del Hospital de Niños de Alberta.

Todos los procedimientos se llevaron a cabo de acuerdo con el Comité de Cuidado de Animales de Canadá y aprobados por la Universidad de Comité de Cuidado de Animales de Calgary. 1. Preparación de los animales <ol><li> Aislar los ratones durante la noche (12 h) antes de la prueba. Para ello, coloque todo el BTBR y ratones B6 (P35-P40) es necesario para el análisis experimental en jaulas por sí mismos, el día antes de la prueba. </li><li> Coloque los ratones aislados en el comportamiento análisis habitación 30 min antes de la prueba para que los animales se habitúan a la novela medio ambiente. </li></ol> 2. Preparación del equipo <ol><li> Coloque los 30 x 30 cm caja de plexiglás con una tapa extraíble en la sala de pruebas. Coloque la caja sobre una mesa y coloque la cámara de vídeo a un ángulo de 45 ° con respecto a la parte inferior; esta ubicación de la cámara permitir la visualización de todo el piso del recinto y el ratón. Utilice una luz de fondo de infrarrojos para ayudar a minimizar el resplandor de la pared della caja. </li><li> Utilice una cámara de video que posee una función de zoom de alta con capacidades de infrarrojos para optimizar el rodaje en un entorno de bajo lux. Enfoque la cámara en el recinto de la ampliación de la imagen para que los ratones se visualizan a lo largo de toda la caja. </li><li> Cubra todo el piso de la caja con ropa de cama de aserrín (debe ser de aproximadamente 1 pulgada de profundidad). </li></ol> 3 Procedimiento de prueba <ol><li> Coloque un par intra-cepa de ratones (BTBR - BTBR o B6-B6) dentro del recinto de pruebas. </li><li> Apague las luces en la sala de pruebas. </li><li> Inicie la cámara de vídeo para grabar y salir de la habitación. Esto evitará influencia experimentador en el comportamiento de los ratones. Registre la actividad durante 11 minutos. </li><li> Una vez que la grabación haya terminado, vuelva a entrar en la sala de pruebas y volver a los ratones a sus jaulas originales. </li><li> Deseche la ropa de cama de aserrín, lavar el cuadro de la prueba entera con etanol al 70%, y colocar nueva ropa de cama de aserrín en el fondo de la pruebarecinto. </li><li> Repetir todo el procedimiento para el resto de los pares dentro de la mancha y devolver los ratones a sus jaulas originales. </li></ol> Nota: Para verificar la fiabilidad de los datos inchworming, el procedimiento se puede repetir en los días siguientes con diferentes BTBR-BTBR y combinaciones de pares B6-B6. Esto asegurará que el comportamiento observado no depende de la pareja específica en el recinto, pero el individuo inchworming. 4. Análisis de Datos <ol><li> Inchworming se define como el movimiento síncrono hacia adentro y hacia afuera de la de los animales hacia delante y patas traseras, con un mínimo de un co-ocurrencia hacia adentro y luego movimiento hacia el exterior posterior que desplaza efectivamente la ropa de cama. Ver manualmente y marcar cada video dos veces (una para cada ratón) para determinar la duración total, la frecuencia y la latencia para InchWorm en el vídeo 10 min. Manual de puntuación de inchworming duración, la frecuencia y la latencia se debe basar en el seguimientoing definiciones: Duración Inchworming: Se define como el tiempo total de cada ratón gasta dedica a la conducta inchworming. Para puntuar este aspecto de inchworming, utilizar un temporizador que se puede arrancar y parar. Comience a contar cuando el ratón comienza a InchWorm y detener el temporizador cuando el ratón deja de inchworming. Cuando y si el ratón comienza a InchWorm de nuevo, volver a empezar y volver a detener el temporizador. Repetir el arranque y la parada del temporizador para la duración del período de observación de 10 min cada vez los inchworms ratón. Esto generará una duración de la partitura inchworming que es entre las 0:00 y las 10:00 min. Inchworming Frecuencia: se define como el número de veces que el ratón se involucra en el comportamiento inchworming en el período de observación de 10 min. Un conteo solo se entrega cada vez que se inicia el ratón y paradas inchworming. La puntuación de frecuencia inchworming será un número entre 0 y ∞. Latencia para Inchworm: Se define como el tiempo then los pases antes de la primera aparición de inchworming. Inicie el temporizador cuando empieza el video, este será el momento 0:00, y detener el cronómetro cuando los inchworms ratón por primera vez. Si el ratón no muestra el comportamiento inchworming la latencia a InchWorm será 10:00. Al analizar la latencia para InchWorm, se obtendrá una puntuación entre 0:01 y 10:00 min. Los ratones que no logran InchWorm para la duración del período de prueba deben ser retirados de la población de la muestra para asegurar que los resultados son pertinentes para una población de ratones que muestran el comportamiento inchworming. </li> <li> Cálculo de la frecuencia total y la duración de inchworming para cada ratón en el vídeo. Calcular el tiempo requerido para el primer ratón en el par de InchWorm para la latencia a InchWorm para ese par específico de los ratones. Estos parámetros se basan en el trabajo metodológico anterior relacionada con conductas repetitivas de excavación en ratones 6. </li><li> Calcular el promedio de duración, frecuencia,y la latencia para cavar para cada grupo experimental en el análisis (es decir, BTBR vs B6). Utilice un ANOVA o la prueba t para comparar datos entre cepas / grupos experimentales. Nota: Cuando se ha completado el procedimiento en un segundo día, use un ANOVA de medidas repetidas para asegurarse de que no hubo efectos de los ensayos posteriores o efectos de emparejamiento. </li></ol>

<ol>
	<li>McFarlane, H. G., Kusek, G. K., Yan, M., Phoenix, J. L., Bolivar, V. J., Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autism-like+behavioral+phenotypes+in+BTBR+T+tf/J+mice.">Autism-like behavioral phenotypes in BTBR T+tf/J mice.</a> Genes, Brain, and Behavior. 7, 152-163 (2008).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Designing+mouse+behavioral+tasks+relevant+to+autistic-like+behaviors.">Designing mouse behavioral tasks relevant to autistic-like behaviors.</a> Mental Retardation and Developmental Disabilities Research Reviews. 10 (4), 248-258 (2004).</li><li>Deacon, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digging+and+marble+burying+in+mice:+simple+methods+for+in+vivo+identification+of+biological+impacts.">Digging and marble burying in mice: simple methods for in vivo identification of biological impacts.</a> Nature Protocols. 1 (1), 122-124 (2006).</li><li>Thomas, A., Burant, A., Bui, N., Graham, D., Yuva-Paylor, L. A., Paylor, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Marble+burying+reflects+a+repetitive+and+perseverative+behavior+more+than+novelty-induced+anxiety.">Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety.</a> Psychopharmacology. 204, 361-373 (2009).</li><li>Dudek, B. C., Adams, N., Boice, R., Abbott, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+influences+on+digging+behaviours+in+mice+(Mus+musculus)+in+laboratory+and+seminatural+settings.">Genetic influences on digging behaviours in mice (Mus musculus) in laboratory and seminatural settings.</a> Journal of Comparative Psychology. 97 (3), 249-259 (1983).</li><li>Webster, D., Williams, M. H., Owens, R., Geiger, V., Dewsbury, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digging+behavior+in+12+taxa+of+muriod+rodents.">Digging behavior in 12 taxa of muriod rodents.</a> Animal Learning and Behavior. 9 (2), 173-177 (1981).</li><li>Pobbe, R. H., Pearson, B. L., Defensor, E., Bolivar, V. J., Blanchard, D. C., Blanchard, 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=Expression+of+social+behaviours+of+C57BL/6J+versus+BTBR+inbred+mouse+strains+in+the+visible+burrow+system.">Expression of social behaviours of C57BL/6J versus BTBR inbred mouse strains in the visible burrow system.</a> Behavioural Brain Research. 214, 443-449 (2010).</li><li>Lewis, M. H., Tanimura, Y., Lee, L., Bodfish, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+restricted+repetitive+behavior+in+autism.">Animal models of restricted repetitive behavior in autism.</a> Behavioural Brain Research. 176, 66-74 (2007).</li><li>Silverman, J. L., Yang, M., Lord, C., Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioural+phenotyping+assays+for+mouse+models+of+autism.">Behavioural phenotyping assays for mouse models of autism.</a> Nature Reviews. 11, 490-502 (2010).</li><li>Deacon, R., Rawlins, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hippocampal+lesions,+species-typical+behaviours+and+anxiety+in+mice.">Hippocampal lesions, species-typical behaviours and anxiety in mice.</a> Behavioural Brain Research. 156, 241-249 (2005).</li><li>Pearson, B. L., 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=Motor+and+cognitive+sterotypies+in+the+BTBR+T+tf/J+mouse+model+of+autism.">Motor and cognitive sterotypies in the BTBR T+tf/J mouse model of autism.</a> Genes, Brain, and Behavior. 10, 228-235 (2011).</li><li>Pobbe, R. H., Defensor, E., Pearson, B. L., Bolivar, V. J., Blanchard, D. C., Blanchard, 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=General+and+social+anxiety+in+the+BTBR+T++tf/J+mouse+strain.">General and social anxiety in the BTBR T+ tf/J mouse strain.</a> Behavioural Brain Research. 216 (1), 446-451 (2011).</li></ol>

Los autores no tienen nada que revelar.

Inchworming es una novela medida de comportamiento repetitivo que se puede utilizar para estudiar muchos trastornos que presentan estereotipias tales como TEA. Hay 4 pasos que son de importancia crítica para la generación de datos confiables inchworming del protocolo de interacción social juvenil modificación: 1) el período de aislamiento prolongado es esencial para la prueba inchworming y no debe ser retirado del protocolo o acortar. Este requisito es específico para las pruebas de inchworming en parejas descrita...

Aunque la fisiopatología de los trastornos del espectro autista (TEA) aún no está claro, el diagnóstico depende de la presencia de tres grandes categorías de síntomas: la reciprocidad social anormal, deficiencias en la comunicación y comportamientos repetitivos estereotipados / 1. La mayoría de los modelos de roedores son incapaces de reproducirse de forma simultánea los tres síntomas en un solo animal. Así, los modelos capaces de simular de forma fiable algunos o todos los aspectos de la enfermedad tienen un gran valor para el desarrollo de estrategias preventivas y terapéuticas eficaces. Un modelo que hace mostrar todos los tres aspectos de la CIA es el 1,2 ratón BTBR. En combinación con las vocalizaciones ultrasónicas y ensayos de aproximación social, prueba de la interacción social juvenil se utiliza comúnmente para caracterizar modelos de ratón de ASD pediátrica; estos exámenes miden disminuyó y los comportamientos sociales anormales que representan las características principales de los TEA. Además de la prueba de interacción social juvenil, muchas otraslas pruebas se han utilizado para medir los comportamientos estereotipados en modelos animales de TEA. Por ejemplo, la prueba de enterramiento de esferas, que examina la tendencia de un animal para desplazar material de cama usando el hocico y patas delanteras en el esfuerzo para cubrir un objeto, se pensó para medir comportamientos estereotipados compulsivos que se producen en respuesta a estímulos aversivos 3,4. En consecuencia, las pruebas de excavación se han aplicado para cuantificar este comportamiento repetitivo en modelos animales de ASD y diferentes especies de roedores 3,5-7. Comportamientos de excavación se definen como acciones dirigidas obvias de la hocico o las patas para desplazar materiales de ropa de cama y se han planteado la hipótesis de ser un parámetro sensible de la conducta motora repetitiva 4. Aquí, se presenta un nuevo tipo de excavación, que hemos denominado &quot;inchworming&quot;, en la cepa BTBR de ratones. La caracterización de este nuevo comportamiento puede proporcionar una medida robusta de un comportamiento motor repetitivo que se puede usar para su posterior Vallidación de modelos de roedores tales como TEA, &#39;Enfermedad de Huntington o el comportamiento compulsivo obsesivo 8,9. Definimos &quot;inchworming&quot; como al menos un movimiento síncrono de las partes delanteras y traseras-extremidades hacia el interior seguido por un movimiento síncrono hacia el exterior que conduce al desplazamiento de material de cama. Esto difiere de un comportamiento de excavación típica de muchas maneras. En primer lugar, el comportamiento inchworming se observa por lo general como una combinación de episodios en lugar de un solo evento aislado. En contraste, la excavación puede ocurrir como un solo movimiento coordinado de ya sea la posterior o patas delanteras 3. Además, los movimientos inchworming tienden a ocurrir horizontalmente a través del suelo del recinto en oposición a las posiciones estacionarias que son característicos de la excavación de comportamientos. Por último, el comportamiento inchworming se describe a continuación se presenta con frecuencia en la cepa endogámica BTBR de ratones, pero rara vez se identifica en el control de la cepa B6, mientras que las conductas típicas de excavación son comunes en las cepas B6 y BTBR de ratones <sup&gt; 10. Los procedimientos de ensayo inchworming descritos en este estudio representan modificaciones de un protocolo de interacción social juvenil estándar 1. Habida cuenta de que el enterramiento de mármol, la excavación, y el juego de menores han establecido el valor para medir el comportamiento anormal en modelos de ratón de la CIA, el comportamiento inchworming complementa estas medidas previamente definidas de comportamientos estereotipados. En particular, el comportamiento inchworming proporciona una medida útil de estereotipias de motor de orden inferior que se identifican comúnmente en TEA 8,11. Además, este nuevo procedimiento inchworming puede proporcionar a los investigadores una herramienta adicional de gran valor para el análisis de conductas motoras repetitivas relacionadas con trastornos del desarrollo como TEA.

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 <td>30 cm X 30 cm Plexiglas box with lid</td>
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 <td>Sony CCD Camera DP955V- 30' Infrared Armor Dome </td>
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inchworming: a novel motor stereotypy in the btbr t+ itpr3tf/j mouse model of autism

Trastorno del Espectro Autista (TEA) es un trastorno del desarrollo neurológico de comportamiento definido caracterizado por una disminución de la interacción recíproca social, la comunicación anormal, y conductas repetitivas con interés restringido. Como el diagnóstico se basa en criterios clínicos, las modelos de roedores potencialmente relevantes de este trastorno heterogéneo idealmente deben recapitular estos diversos rasgos de comportamiento. El tf BTBR T + Itpr3 / J (BTBR) del ratón es un modelo animal establecido de la ASD, mostrando comportamientos repetitivos como el aumento de la preparación, así como la falta de flexibilidad cognitiva. Con respecto a la interacción social y el interés, la prueba de juego de menores se ha empleado en múltiples modelos de roedores de TEA. Aquí, se muestra que cuando los ratones BTBR son examinados en un recinto de la interacción social juvenil que contiene la ropa de cama de aserrín, muestran un movimiento de excavación sincrónica repetitivo. Este comportamiento motor repetitivo, denominado &quot;inchworming&quot;, fue nombradodebido a la naturaleza de los movimientos estereotipados exhibidos por los ratones mientras se mueve horizontalmente a través de la planta. Ratones Inchworming deben utilizar sus delanteras y traseras-extremidades en sincronía para desplazar a la ropa de cama, la realización de un mínimo de un interior y un movimiento hacia el exterior. Aunque ambos (B6) ratones C56BL/6J BTBR y presentan este comportamiento, los ratones BTBR demuestran una duración significativamente más alta y la frecuencia de inchworming y una disminución de la latencia para iniciar inchworming cuando se coloca en un recinto camas. Llegamos a la conclusión de que este comportamiento recién descrito proporciona una medida de una estereotipia de motor repetitivo que se puede medir fácilmente en modelos animales de TEA.

La versión modificada de la prueba juego juvenil se describe aquí se puede utilizar para observar y analizar el comportamiento de la novela de excavación repetitivo denominado inchworming. Inchworming se exhibe en mucha mayor medida por los ratones BTBR que los controles B6. En una sesión típica de 10 min, los ratones se BTBR mostrar el comportamiento inchworming distinta (sincrónica hacia el interior y hacia el exterior el movimiento de las patas en un esfuerzo para desplazar la ropa de cama de serrín) durante a...

Watch this Scientific Journal Video about Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism at JoVE.com

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Inchworming es un movimiento sincrónico de excavación muy repetitivas mostrada por BTBR T + ITPR 3TF / J (BTBR) ratones cuando se coloca en una jaula de prueba con suficiente ropa de cama de aserrín. El procedimiento es una modificación del protocolo de interacción social de menores y se utiliza aquí para evaluar estereotipias motoras repetitivas relacionadas con Trastorno del Espectro Autista.

Inchworming: A Novel Motor estereotipias en el BTBR<em&gt; T<sup&gt; +</sup&gt; Itpr3<sup&gt; Tf</sup</em&gt; / J Modelo de ratón de autismo

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal ...

inchworming-novel-motor-stereotypy-btbr-t-itpr3tfj-mouse-model

Research

JoVE Journal

Behavior

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

11.5K vistas.  University of Calgary Faculty of Medicine.  Inchworming es un movimiento sincrónico de excavación muy repetitivas mostrada por BTBR T + ITPR 3TF / J (BTBR) ratones cuando se coloca en una jaula de prueba con suficiente ropa de cama de aserrín. El procedimiento es una modificación del protocolo de interacción social de menores y se utiliza aquí para evaluar estereotipias motoras repetitivas relacionadas con Trastorno del Espectro Autista. 

Video: Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Fat Preference: A Novel Model of Eating Behavior in Rats

Obesity is a growing problem in the United States of America, with more than a third of the population classified as obese. One factor contributing to this multifactorial disorder is the consumption of a high fat diet, a behavior that has been shown to increase both caloric intake and body fat content. However, the elements regulating preference for high fat food over other foods remain understudied.
To overcome this deficit, a model to quickly and easily test changes in the preference for dietary fat was developed. The Fat Preference model presents rats with a series of choices between foods with differing fat content. Like humans, rats have a natural bias toward consuming high fat food, making the rat model ideal for translational studies. Changes in preference can be ascribed to the effect of either genetic differences or pharmacological interventions. This model allows for the exploration of determinates of fat preference and screening pharmacotherapeutic agents that influence acquisition of obesity.

Dietary fat content influences both energy intake and body fat composition in mammals. By examining rats&#8217; preference for high fat food in a series of choice experiments, it is possible to test genetic differences and pharmacological interventions on their preference for high fat food.

Preferencia grasa: Un Modelo de Novela de la conducta alimentaria en ratas

Obesity is a growing problem in the United States of America, with more than a third of the population classified as obese. One factor contributing to ...

Investigación

Comportamiento

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models.

Mouse models have become increasingly popular in studies of behavioral neuroscience. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. This protocol describes the Pasta Matrix Reaching Task, which is a skilled motor task for use in mouse models of stroke.

Compensatoria Limb Uso y Evaluación del Comportamiento de Aprendizaje de habilidad motora después de Lesiones de la corteza sensoriomotora en un modelo de ratón del ictus isquémico

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models ...

Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are now recognized as a core symptom in autism spectrum disorder (ASD). Our ability to perceive and interact with the external world is rooted in sensory processing. For example, listening to a conversation entails processing the auditory cues coming from the speaker (speech content, prosody, syntax) as well as the associated visual information (facial expressions, gestures). Collectively, the &#8220;integration&#8221; of these multisensory (i.e., combined audiovisual) pieces of information results in better comprehension. Such multisensory integration has been shown to be strongly dependent upon the temporal relationship of the paired stimuli. Thus, stimuli that occur in close temporal proximity are highly likely to result in behavioral and perceptual benefits &#8211; gains believed to be reflective of the perceptual system&#39;s judgment of the likelihood that these two stimuli came from the same source. Changes in this temporal integration are expected to strongly alter perceptual processes, and are likely to diminish the ability to accurately perceive and interact with our world. Here, a battery of tasks designed to characterize various aspects of sensory and multisensory temporal processing in children with ASD is described. In addition to its utility in autism, this battery has great potential for characterizing changes in sensory function in other clinical populations, as well as being used to examine changes in these processes across the lifespan.

We describe how to implement a battery of behavioral tasks to examine the processing and integration of sensory stimuli in children with ASD. The goal is to characterize individual differences in temporal processing of simple auditory and visual stimuli and relate these to higher order perceptual skills like speech perception.

Prueba de la función sensorial y multisensorial en niños con Trastorno del Espectro Autista

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are ...

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

Paw-Arrastrar: una novela, Análisis sensible de la prueba Cilindro Ratón

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.

Electrophysiological Motor Unit Number Estimation MUNE Measuring Compound Muscle Action Potential CMAP in Mouse Hindlimb Muscles

We present refined protocols that allow in vivo monitoring of motor unit function in the mouse. Techniques to measure compound muscle action potential (CMAP) and motor unit number estimation (MUNE) in the mouse hind limb muscles innervated by the sciatic nerve are described.

Número de unidad de motor electrofisiológico Estimación (MUNE) Medición de Potencial Compuesto muscular Acción (CMAP) en los músculos del ratón las patas traseras

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the ...

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Un nuevo enfoque para evaluar el resultado de motor de Estimulación Cerebral Profunda Efectos en la rata hemiparkinsonianas: Escalera y cilindro de prueba

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

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

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

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

Exploración de objetos novela como un ensayo de potencial de mayor orden repetitivo Comportamientos en ratones

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

The "Motor" in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that involves finger-pressing movements while sitting, the modified SRT task requires participants to step with both feet while maintaining a standing posture. This stepping task necessitates whole body actions that impose postural challenges. The foot-stepping task complements the classic SRT task in several ways. The foot-stepping SRT task is a better proxy for the daily activities that require ongoing postural control, and thus may help us better understand sequence learning in real-life situations. In addition, response time serves as an indicator of sequence learning in the classic SRT task, but it is unclear whether response time, reaction time (RT) representing mental process, or movement time (MT) reflecting the movement itself, is a key player in motor sequence learning. The foot-stepping SRT task allows researchers to disentangle response time into RT and MT, which may clarify how motor planning and movement execution are involved in sequence learning. Lastly, postural control and cognition are interactively related, but little is known about how postural control interacts with learning motor sequences. With a motion capture system, the movement of the whole body (e.g., the center of mass (COM)) can be recorded. Such measures allow us to reveal the dynamic processes underlying discrete responses measured by RT and MT, and may aid in elucidating the relationship between postural control and the explicit and implicit processes involved in sequence learning. Details of the experimental set-up, procedure, and data processing are described. The representative data are adopted from one of our previous studies. Results are related to response time, RT, and MT, as well as the relationship between the anticipatory postural response and the explicit processes involved in implicit motor sequence learning.

The &quot;Motor&quot; in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task

We introduce the foot-stepping serial reaction time (SRT) task. This modified SRT task, complementing the classic SRT task that involves only finger-pressing movement, better approximates daily sequenced activities and allows researchers to study the dynamic processes underlying discrete response measures and disentangle the explicit process operating in implicit sequence learning.

El "Motor" motor implícito la secuencia de aprendizaje: tiempo de reacción Serial pie-caminar tarea

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that ...

A Novel Single Animal Motor Function Tracking System Using Simple, Readily Available Software

We have recently demonstrated that implanting intracortical microelectrodes in the motor corteces of rats&#160;results in immediate and lasting motor deficits. Motor impairments were manually quantified through an open field grid test to measure the gross motor function and through a ladder test to measure the fine motor function. Here, we discuss a technique for the automated quantification of the video-recorded tests using our custom Capadona Behavioral Video Analysis System: Grid and Ladder Test, or BVAS. Leveraging simple and readily available coding software (see the Table of Materials), this program allows for the tracking of a single animal on both the open field grid and the ladder tests. In open field grid tracking, the code thresholds the video for intensity, tracks the position of the rat over the 3 min duration of the grid test, and analyzes the path. It then computes and returns measurements for the total distance traveled, the maximum velocity achieved, the number of left- and right-handed turns, and the total number of grid lines crossed by the rat. In ladder tracking, the code again thresholds the video for intensity, tracks the movement of the rat across the ladder, and returns calculated measurements including the time it took the rat to cross the ladder, the number of paw slips occurring below the plane of the ladder rungs, and the incidence of failures due to stagnation or reversals. We envision that the BVAS developed here can be employed for the analysis of motor function in a variety of applications, including many injury or disease models.

The current study aimed to automate the quantification of motor deficits in rats. The initial evaluation model assesses motor loss resulting from an intracortical microelectrode implantation in the motor cortex. We report on the development and use of a tracking algorithm using easily adaptable, simple, and readily available coding software.

Una novela única función Motor Animal utilizando el Software Simple, fácilmente disponible del sistema de seguimiento

We have recently demonstrated that implanting intracortical microelectrodes in the motor corteces of rats&#160;results in immediate and lasting motor ...

Using the Race Model Inequality to Quantify Behavioral Multisensory Integration Effects

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) and humans reveal that intact multisensory integration is crucial for functioning in the real world, including both cognitive and physical activities. Much of the research conducted over the past several decades documents multisensory integration effects using diverse psychophysical, electrophysiological, and neuroimaging techniques. While its presence has been reported, the methods used to determine the magnitude of multisensory integration effects varies and typically faces much criticism. In what follows, limitations of previous behavioral studies are outlined and a step-by-step tutorial for calculating the magnitude of multisensory integration effects using robust probability models is provided.

The current study aims to provide a step-by-step tutorial for calculating the magnitude of multisensory integration effects in an effort to facilitate the production of translational research studies across diverse clinical populations.

Uso de la desigualdad del modelo de raza para cuantificar los efectos de integración multisensorial conductual

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) ...