Este trabajo es apoyado por una beca (1R01MH094449-01A1) del Instituto Nacional de Salud Mental de YZ

Los experimentos descritos en este manuscrito se realizaron de acuerdo con las directrices y normas establecidas por la Universidad de California, Santa Cruz Institucional Cuidado de Animales y el empleo Comisión. 1. Configuración (Véase también Lista de Materiales) <ol><li> Utilice semillas de mijo como bolitas de comida. </li><li> Utilice una clara cámara de formación de plexiglás hechos a medida (20 cm de alto, 15 cm de profundidad, y 8,5 cm de ancho, medido desde el exterior, con el espesor de la plexiglás 0,5 cm) que contiene tres ranuras verticales (una hendidura en el borde &#39;dar forma&#39;, y dos ranuras en el borde opuesto &quot;formación&quot;). Las ranuras verticales deben ser 0,5 cm de ancho y 13 cm de altura y ser situado en la pared frontal de la caja: en el centro, en el lado izquierdo, y en el lado derecho (Figura 1A). </li><li> Utilice una bandeja inclinada para mantener las semillas utilizadas durante las sesiones que configuran. La bandeja puede ser por encargo a partir de tres láminas de vidrio (fig. 1B). </li><li> Prepare una plataforma de alimentos (8,5 cm de largo, 4,4 cm de ancho, y 0,9 cm de altura). Esta plataforma comida se coloca en la parte frontal (frente al entrenador) de la cámara de formación durante las sesiones de entrenamiento. Hay dos ranuras divot sobre la plataforma de alimentación para las semillas de posicionamiento, una ranura a la izquierda, y la otra ranura en el lado derecho. Las chuletas son 0,3 cm del borde largo y 2,4 cm del borde ancho (Figura 1C). La ranuras divot izquierdo y derecho corresponden a la ranura izquierda y derecha en la cámara de formación de ratón y se utilizan para el entrenamiento de los miembros delanteros dominantes. El propósito de tener estas ranuras divot es para asegurar que la semilla se coloca constantemente en el mismo lugar para cada intento de alcanzar. </li><li> Durante las sesiones tienen en la mano un par de pinzas, balanza, y cronómetro. </li></ol> 2. Privación de alimentos (2 días) <ol><li> Pese cada ratón para obtener un peso corporal basal antes de la privación de alimentos. </li><li> Food-restringir los ratones durante 2 días para iniciar peso corporalpérdida. Como punto de partida general, los ratones se les da 0.1 g de alimento por 1 g de peso corporal por día (por ejemplo, un ratón que pesa 15 g, por lo general se inicia con 1,5 g de alimento). Ajustar la cantidad de alimento basado en el peso corporal de línea de base, la tasa de pérdida de peso, el sexo y la edad de los ratones. Mientras que el peso corporal puede continuar para disminuir un poco más durante la fase de conformación, tales peso corporal reducido (es decir, ~ 90% del peso línea de base original) debe mantenerse a lo largo de la formación (Figuras 2A y 2B). La cantidad de alimento necesaria para mantener el peso corporal del ratón es típicamente la misma que la cantidad utilizada en la restricción. </li></ol> 3. Shaping (3-7 días) <ol><li> Aclimatación hábitat Grupo (Día 1): Poner dos ratones en la cámara de formación al mismo tiempo. Coloque aproximadamente 20 semillas / ratón dentro de la cámara para su consumo. Permita que los ratones permanezcan en la cámara durante 20 minutos y luego poner de nuevo en su casajaula. </li><li> Aclimatación individual hábitat (Día 2): la misma configuración que en el paso 3.1, pero los ratones lugar en la cámara de formación individual. El propósito del grupo y aclimatación individuo hábitat es conseguir que los ratones están familiarizados tanto con la cámara de la formación y las semillas de mijo. </li><li> Determinación de la posición dominante de la extremidad anterior (día 3 y posteriores): Coloque el lado de hendidura única de la cámara de la formación orientada hacia abajo (Figura 1D). Llene la bandeja de comida con las semillas. Pulse la bandeja de comida contra la pared frontal de la cámara de formación para permitir que las semillas accesible para el ratón. Coloque los ratones en la jaula de forma individual. Si son suficientemente interesado en las semillas situadas en la bandeja de comida, que serían arado a través de la rendija para obtener la semilla en su interior. A continuación, recoger las semillas y los consuma. &quot;Shaping&quot; se considera terminada cuando se cumplen las dos de los siguientes criterios: 1) el ratón realiza 20 intentos que llegan dentro de 20 minutos, y 2) más del 70% alcances son performed con una extremidad anterior. </li></ol> Notas: <ol><li> Si el ratón utiliza su lengua para obtener las semillas dentro de la cámara, mueva de nuevo la bandeja de la ranura ligeramente. El aumento de la distancia de llegar desalienta el ratón para utilizar su lengua para adquirir la semilla y por lo tanto facilita su extremidad anterior alcanzando. </li><li> Si el ratón no puede terminar la conformación dentro de una semana, la caída desde el experimento. </li></ol> 4. Formación (8 + días) <ol><li> Coloque el lado de la doble rendija de la cámara de la formación orientada hacia abajo (Figura 1E). </li><li> Coloque los ratones en la jaula de forma individual. Ponga las semillas individuales en la plataforma de los alimentos en el divot correspondiente a la pata preferido (es decir, para el ratón de mano derecha, utilice la ranura en el lado derecho del ratón). </li><li> Observar el comportamiento de alcanzar ratón y marcar de acuerdo con las siguientes categorías: <ol><li> Éxito: El ratón llega con la pata preferente, agarra y retrieves la semilla, y la inyecta a la boca. </li><li> Caída: El ratón llega con la pata preferente, agarra la semilla, pero la deja caer antes de ponerlo en su boca. </li><li> Falla: El ratón llega con la pata preferente hacia la semilla, pero tampoco alcanza la semilla o llama, se fuera de la placa de sujeción. </li></ol></li><li> Capacitar a los ratones durante 30 intentos alcance sobre el miembro preferido o 20 minutos (lo que ocurra primero) por día. </li><li> Coloca los ratones de vuelta a su jaula después de entrenar y proporcionar cuántica comida diaria. </li></ol> Notas: <ol><li> En algunos casos, los ratones alcanzan incluso cuando no hay semillas colocado en la plataforma de alimentación. Estos alcances son considerados &quot;-en vano alcances&quot; y no se cuentan para el número total de intentos de alcance. Para desalentar &quot;-en vano alcances&quot;, los ratones del tren a caminar de vuelta al otro extremo de la cámara de formación antes de colocar la siguiente siembra. Una estrategia similar ha sido utilizado en la ratas para una tarea de comportamiento similares 21. Los ratones a veces también llegan con la pata no preferido en presencia de la semilla. Estos alcances se consideran &#39;alcances&#39; contralateral y no cuentan para el número total de partes más tampoco. </li><li> Para limitar las variaciones del comportamiento debidos a las fluctuaciones en el ritmo circadiano, lleve a cabo todas las sesiones de la conformación y capacitación al mismo momento del día, durante las horas normales de vigilia para los ratones. </li><li> Para evitar la variación del comportamiento debido a los diferentes entrenadores, asegúrese de que la misma persona se entrena los mismos ratones durante todo el experimento. </li><li> La atención de los ratones es crítico para esta prueba de comportamiento. Capacitar a los ratones en una habitación separada y tranquila para reducir al mínimo la perturbación del medio ambiente. </li><li> Los ratones pueden ser capacitados con más de 30 alcanza al día (por ejemplo, 50 tramos). Aumentar el número de intentos que alcanzan permite examinar la mejora del comportamiento dentro de la misma sesión de entrenamiento. </li></ol> 5. DatUna cuantificación Hay muchas maneras de cuantificar el comportamiento del ratón después de la capacitación. Dos análisis más directo son: <ol><li> Tasa de éxito = alcances más exitosos intentos alcanzando el total, que se presentan como porcentajes. Las tasas de abandono y fracaso se pueden trazar la misma manera. </li><li> Velocidad de éxito = número de intentos exitosos dividido por el tiempo, presentó alcances como exitosas por minuto. En la mayoría de los casos, la velocidad de éxito sigue aumentando, incluso cuando la tasa de éxito alcanza la meseta. </li></ol>

<ol>
	<li>Schmidt, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+Learning+Principles+for+Physical+Therapy.">Motor Learning Principles for Physical Therapy.</a> Foundations for Physical Therapy. Contemporary Management of Motor Control Problems, Proceedings of the II STEP Conference. , 49-63 (1991).</li><li>Honda, M., Deiber, M. P., Ibanez, V., Pascual-Leone, A., Zhuang, P., Hallett, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+cortical+involvement+in+implicit+and+explicit+motor+sequence+learning.+A+PET+study..">Dynamic cortical involvement in implicit and explicit motor sequence learning. A PET study..</a> Brain. 121, 2159-2173 (1998).</li><li>Karni, A., Meyer, G., Jezzard, P., Adams, M. M., Turner, R., Ungerleider, L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+MRI+evidence+for+adult+motor+cortex+plasticity+during+motor+skill+learning.">Functional MRI evidence for adult motor cortex plasticity during motor skill learning.</a> Nature. 377, 155-158 (1995).</li><li>Karni, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+acquisition+of+skilled+motor+performance:+fast+and+slow+experience-driven+changes+in+primary+motor+cortex.">The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex.</a> Proc. Natl Acad. Sci. U.S.A. 95, 861-868 (1998).</li><li>Muellbacher, W., 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=Early+consolidation+in+human+primary+motor+cortex.">Early consolidation in human primary motor cortex.</a> Nature. 415, 640-644 (2002).</li><li>Kleim, J. A., Hogg, T. M., VandenBerg, P. M., Cooper, N. R., Bruneau, R., Remple, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+synaptogenesis+and+motor+map+reorganization+occur+during+late,+but+not+early,+phase+of+motor+skill+learning.">Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning.</a> J. Neurosci. 24, 628-633 (2004).</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=Learning-induced+LTP+in+neocortex.">Learning-induced LTP in neocortex.</a> 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> Nat. Neurosci. 1, 230-234 (1998).</li><li>Farr, T. D., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+and+qualitative+impairments+in+skilled+reaching+in+the+mouse+(Mus+musculus)+after+a+focal+motor+cortex+stroke.">Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke.</a> Stroke J. Cereb. Circ. 33, 1869-1875 (2002).</li><li>Huang, V. S., Haith, A., Mazzoni, P., Krakauer, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rethinking+motor+learning+and+savings+in+adaptation+paradigms:+model-free+memory+for+successful+actions+combines+with+internal+models.">Rethinking motor learning and savings in adaptation paradigms: model-free memory for successful actions combines with internal models.</a> Neuron. 70, 787-801 (2011).</li><li>Smith, M. A., Ghazizadeh, A., Shadmehr, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interacting+adaptive+processes+with+different+timescales+underlie+short-term+motor+learning.">Interacting adaptive processes with different timescales underlie short-term motor learning.</a> PLoS Biol. 4, (2006).</li><li>Pavlides, C., Miyashita, E., Asanuma, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Projection+from+the+sensory+to+the+motor+cortex+is+important+in+learning+motor+skills+in+the+monkey.">Projection from the sensory to the motor cortex is important in learning motor skills in the monkey.</a> J. Neurophysiol. 70, 733-741 (1993).</li><li>Paz, R., Boraud, T., Natan, C., Bergman, H., Vaadia, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparatory+activity+in+motor+cortex+reflects+learning+of+local+visuomotor+skills.">Preparatory activity in motor cortex reflects learning of local visuomotor skills.</a> Nat. Neurosci. 6, 882-890 (2003).</li><li>Paz, R., Vaadia, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Learning-induced+improvement+in+encoding+and+decoding+of+specific+movement+directions+by+neurons+in+the+primary+motor+cortex.">Learning-induced improvement in encoding and decoding of specific movement directions by neurons in the primary motor cortex.</a> PLoS Biol. 2, (2004).</li><li>Plautz, E. J., Milliken, G. W., Nudo, 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=Effects+of+repetitive+motor+training+on+movement+representations+in+adult+squirrel+monkeys:+role+of+use+versus+learning.">Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning.</a> Neurobiol. Learn. Mem. 74, 27-55 (2000).</li><li>Hosp, J. A., Pekanovic, A., Rioult-Pedotti, M. S., 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=Dopaminergic+projections+from+midbrain+to+primary+motor+cortex+mediate+motor+skill+learning.">Dopaminergic projections from midbrain to primary motor cortex mediate motor skill learning.</a> J. Neurosci. 31, 2481-2487 (2011).</li><li>Adkins, D. L., Boychuk, J., Remple, M. S., Kleim, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+training+induces+experience-specific+patterns+of+plasticity+across+motor+cortex+and+spinal+cord.">Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord.</a> 101, 1776-1782 (2006).</li><li>Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+endpoint,+descriptive,+and+kinematic+comparison+of+skilled+reaching+in+mice+(Mus+musculus)+with+rats+(Rattus+norvegicus).">An endpoint, descriptive, and kinematic comparison of skilled reaching in mice (Mus musculus) with rats (Rattus norvegicus).</a> Behav. Brain Res. 78, 101-111 (1996).</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>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>Whishaw, I. Q., Whishaw, P., Gorny, B. <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+movement+rating+scale.">The structure of skilled forelimb reaching in the rat: a movement rating scale.</a> J .Vis. Exp. , (2008).</li><li>Bailey, K. R., 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=Anxiety-Related+Behavior+in+Mice.">Anxiety-Related Behavior in Mice.</a> In Buccafusco JJ (Ed.) Methods of Behavior Analysis in Neuroscience. Chapter 5, 2nd ed. , (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> Curr. Opin. Neurobiol. 21, 169-174 (2011).</li><li>Qian, Y., Chen, M., Forssberg, H., Diaz Heijtz, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+variation+in+dopamine-related+gene+expression+influences+motor+skill+learning+in+mice.">Genetic variation in dopamine-related gene expression influences motor skill learning in mice.</a> Genes Brain Behav. 12, 604-614 (2013).</li><li>MacLellan, C. L., Gyawali, S., Colbourne, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Skilled+reaching+impairments+follow+intrastriatal+hemorrhagic+stroke+in+rats.">Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats.</a> Behav. Brain Res. 175, 82-89 (2006).</li><li>Hong, S. 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=Reduced+hippocampal+neurogenesis+and+skill+reaching+performance+in+adult+Emx1+mutant+mice.">Reduced hippocampal neurogenesis and skill reaching performance in adult Emx1 mutant mice.</a> Exp. Neurol. 206, 24-32 (2007).</li><li>Bureau, G., Carrier, M., Lebel, M., Cyr, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intrastriatal+inhibition+of+extracellular+signal-regulated+kinases+impaired+the+consolidation+phase+of+motor+skill+learning.">Intrastriatal inhibition of extracellular signal-regulated kinases impaired the consolidation phase of motor skill learning.</a> Neurobiol. Learn. Mem. 94, 107-115 (2010).</li><li>McCormick, D. A., Lavond, D. G., Thompson, R. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuronal+responses+of+the+rabbit+brainstem+during+performance+of+the+classically+conditioned+nictitating+membrane+(NM)/eyelid+response.">Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response.</a> Brain Res. 271, 73-88 (1983).</li><li>Molinari, 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=Cerebellum+and+procedural+learning:+evidence+from+focal+cerebellar+lesions.">Cerebellum and procedural learning: evidence from focal cerebellar lesions.</a> Brain. 120, 1753-1762 (1997).</li><li>Willuhn, I., Steiner, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor-skill+learning+in+a+novel+running-wheel+task+is+dependent+on+D1+dopamine+receptors+in+the+striatum.">Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum.</a> Neuroscience. 153, 249-258 (2008).</li></ol>

Los autores declaran no tener ningún conflicto de intereses.

Importancia de la fase de conformación: Debido al aumento de la ansiedad de estar en un entorno desconocido, por lo general es difícil para los ratones para ser capacitados en un ambiente novedoso 21,22. Por lo tanto, el objetivo de la formación es familiarizar a los ratones con la cámara de la formación, el formador (es decir, reducir sus niveles de ansiedad), y los requisitos de la tarea (por ejemplo, para identificar las semillas como fuente de alimento). Ot...

Entender los mecanismos de aprendizaje subyacente y la memoria es uno de los mayores retos de la neurociencia. En el sistema motor, la adquisición de nuevas habilidades motoras con la práctica se refiere a menudo como el aprendizaje motor, mientras que el mantenimiento de las habilidades motoras aprendidas anteriormente es considerado como la memoria del motor 1. El aprendizaje de una nueva habilidad motora se refleja generalmente en la mejora del rendimiento del motor deseado con el tiempo, hasta un punto en que la habilidad de motor o bien se perfeccionó o satisfactoria consistente. Para la mayoría de los casos, la memoria del motor adquirido puede persistir durante un largo período de tiempo, incluso en la ausencia de la práctica. En los seres humanos, los estudios de neuroimagen mediante tomografía por emisión de positrones (PET) y la resonancia magnética funcional (fMRI) han demostrado que la corteza motora primaria (M1) cambios de actividad durante la fase de adquisición de las habilidades motoras de aprendizaje 2-4, y la interferencia temporal de la actividad por la M1 baja frecuencia de estimulación magnética transcraneal conduce a signinificativamente perjudica la retención de mejoría en el comportamiento del motor 5. Del mismo modo, la formación específica-extremidad anterior en ratas induce plasticidad funcional y anatómica en el M1, ejemplificada por el aumento tanto de la actividad de c-fos y la relación de sinapsis / neurona en el M1 contralateral a la extremidad anterior entrenado durante la última fase de las habilidades motoras de aprendizaje 6. Por otra parte, un paradigma de formación similar que también fortalece la capa 2/3 conexiones horizontales en el contralateral M1 correspondiente a la extremidad anterior entrenado, lo que resulta en una reducción de la potenciación a largo plazo (LTP) y el aumento de la depresión a largo plazo (LTD) después de ratas adquieren las tareas 7. Dicha modificación sináptica, sin embargo, no se observa en las regiones corticales M1 correspondiente a la extremidad anterior no entrenado o miembros posteriores 8. Alternativamente, cuando el M1 se daña por accidente cerebrovascular, hay deficiencias dramáticas en las extremidades anteriores habilidades motoras específicas 9. Mientras que la mayoría de los estudios sobre el comportamiento de motor se han llevado a cabo en los seres humanos, el monos, y las ratas 2-8,10-17, los ratones se convierten en un sistema de modelo atractivo debido a sus potentes genética y bajo costo. Aquí se presenta un paradigma de aprendizaje motor habilidad forelimb específica: una tarea de llegar a un solo pellet. En este paradigma, los ratones están capacitados para extender sus patas delanteras a través de una estrecha ranura para captar y recuperar bolitas de comida (semillas de mijo) situadas en una ubicación fija, un comportamiento análogo a aprender tiro con arco, dardos lanzar, y pelotas de baloncesto de disparo en humano. Esta tarea de llegar se ha modificado a partir de estudios de ratas anteriores que han mostrado resultados similares entre los ratones y las ratas 18. Utilizando imágenes transcraneal de dos fotones, nuestro trabajo previo ha seguido la dinámica de las espinas dendríticas (estructuras postsinápticas de las sinapsis excitadoras mayoría) en el tiempo durante este entrenamiento. Se encontró que una sola sesión de entrenamiento condujo a un rápido surgimiento de nuevas espinas dendríticas en las neuronas piramidales en la corteza motora contralateral a la extremidad anterior entrenado. Sformación ubsequent de la misma tarea de llegar a estabilizarse preferentemente estas espinas inducida de aprendizaje-, que persistió mucho después de terminada la formación 19. Por otra parte, las espinas que surgieron durante las repeticiones de llegar tarea tendían a agruparse a lo largo de las dendritas, mientras que las espinas que se forman durante la ejecución tándem de alcanzar la tarea y otra tarea motor forelimb específica (es decir, la tarea de manipulación pasta) no se agrupan 20. En el presente vídeo, se describe paso a paso la instalación de este paradigma del comportamiento, de la privación de alimento inicial para dar forma, y ​​para el entrenamiento motor. También se describen los comportamientos comunes de los ratones durante el proceso de ejecución de este paradigma de comportamiento, y cómo se clasifican y se analizaron estos comportamientos. Por último, se discuten las medidas de precaución necesarias para ejercer tal paradigma de aprendizaje y los problemas que pueden encontrarse durante el análisis de datos.

<table border="0" cellpadding="0" cellspacing="0" width="856">
	<colgroup>
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">Training chamber in clear acrylic box</td>
			<td style="width:595px;">For dimensions, see Fig. 1A</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">Tilted tray for shaping</td>
			<td>custom-made from glass slides, see Fig. 1B</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">Food platform for training</td>
			<td>For dimensions, see Fig. 1C</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">Millet seeds&#160;</td>
			<td>filtered from &#8220;Wild Bird Food Dove and Quail Blend Wild Bird Food (All Living Things)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">Forceps</td>
			<td>For placing the seeds</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">A weighing scale</td>
			<td>For daily body weight measurement</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">A stopwatch</td>
			<td>For time measurement during shaping/training sessions</td>
		</tr>
	</tbody>
</table>

study motor skill learning by single-pellet reaching tasks in mice

El alcanzar para y recuperar objetos requieren movimientos motores precisas y coordinadas en la extremidad anterior. Cuando los ratones están capacitados para comprender y recuperar recompensas de comida situados en una ubicación específica, su rendimiento del motor (que se define como la precisión y la velocidad) mejora progresivamente con el tiempo, y las mesetas después del entrenamiento persistente en varias ocasiones. Una vez que tal habilidad de llegar se domina, su posterior mantenimiento no requiere una práctica constante. Aquí presentamos una tarea de llegar a un solo pellet para estudiar la adquisición y mantenimiento de los movimientos de las extremidades anteriores cualificados en ratones. En este video, lo primero que describen el comportamiento de los ratones que se encuentran comúnmente en el aprendizaje y la memoria paradigma y, a continuación, discutimos cómo clasificar estas conductas y cuantificar los resultados observados. Combinado con la genética del ratón, este paradigma se puede utilizar como una plataforma de comportamiento para explorar las bases anatómicas, las propiedades fisiológicas, y mecanismos moleculares de aprendizaje y la memoria.

Curva de aprendizaje: El dominio de una habilidad motora a menudo requiere la práctica persistente en el tiempo. Una curva típica promedio de aprendizaje se compone de dos fases: una fase de adquisición inicial durante el cual la tasa de éxito mejora progresivamente, y una fase de consolidación más tarde, cuando la tasa de éxito alcanza la meseta (Figura 2C). Debe tenerse en cuenta las curvas de aprendizaje de los ratones individuales varían, diferentes ratones tienen d...

Watch this Scientific Journal Video about Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice at JoVE.com

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Práctica persistente mejora la precisión de los movimientos coordinados. Aquí se introduce una tarea de llegar a un solo gránulo, que está diseñado para evaluar el aprendizaje y la memoria de la extremidad anterior de habilidad en ratones.

Estudio Motor Habilidad Aprendizaje por Casa de pellets Tareas Llegar en ratones

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and ...

study-motor-skill-learning-by-single-pellet-reaching-tasks-in-mice

Research

JoVE Journal

Behavior

20.5K vistas.  University of California, Santa Cruz.  Práctica persistente mejora la precisión de los movimientos coordinados. Aquí se introduce una tarea de llegar a un solo gránulo, que está diseñado para evaluar el aprendizaje y la memoria de la extremidad anterior de habilidad en ratones. 

Video: Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

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 ...

Investigación

Comportamiento

Uncovering Beat Deafness: Detecting Rhythm Disorders with Synchronized Finger Tapping and Perceptual Timing Tasks

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson&#8217;s disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Behavioral tasks that allow for the assessment of perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) are presented. Synchronization of finger tapping to the beat of an auditory stimuli and detecting rhythmic irregularities provides a means of uncovering rhythm disorders.

El descubrimiento de golpe Sordera: Trastornos Detección de ritmo con los dedos sincronizada Tapping y tareas de sincronización de percepción

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here ...

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in different areas of their brain for the localization of their seizure focus and eloquent areas. After implantation, the patient must remain in the hospital until the pathological area of brain is found and possibly resected. During this time, these patients offer a unique opportunity to the research community because any number of behavioral paradigms can be performed to uncover the neural correlates that guide behavior. Here we present a method for recording brain activity from intracranial implants as subjects perform a behavioral task designed to assess decision-making and reward encoding. All electrophysiological data from the intracranial electrodes are recorded during the behavioral task, allowing for the examination of the many brain areas involved in a single function at time scales relevant to behavior. Moreover, and unlike animal studies, human patients can learn a wide variety of behavioral tasks quickly, allowing for the ability to perform more than one task in the same subject or for performing controls. Despite the many advantages of this technique for understanding human brain function, there are also methodological limitations that we discuss, including environmental factors, analgesic effects, time constraints and recordings from diseased tissue. This method may be easily implemented by any institution that performs intracranial assessments; providing the opportunity to directly examine human brain function during behavior.

Patients implanted with intracranial electrodes provide a unique opportunity to record neurological data from multiple areas of the brain while the patient performs behavioral tasks. Here, we present a method of recording from implanted patients that can be reproducible at other institutions with access to this patient population.

Realización de tareas de comportamiento en sujetos con intracraneales Electrodos

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in ...

Functional Near Infrared Spectroscopy of the Sensory and Motor Brain Regions with Simultaneous Kinematic and EMG Monitoring During Motor Tasks

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is relatively flexible with respect to participant positioning and allows for some head movements during tasks. Additionally, it is inexpensive, light weight, and portable, with very few contraindications to its use. This presents a unique opportunity to study functional brain activity during motor tasks in individuals who are typically developing, as well as those with movement disorders, such as cerebral palsy. An additional consideration when studying movement disorders, however, is the quality of actual movements performed and the potential for additional, unintended movements. Therefore, concurrent monitoring of both blood flow changes in the brain and actual movements of the body during testing is required for appropriate interpretation of fNIRS results. Here, we show a protocol for the combination of fNIRS with muscle and kinematic monitoring during motor tasks. We explore gait, a unilateral multi-joint movement (cycling), and two unilateral single-joint movements (isolated ankle dorsiflexion, and isolated hand squeezing). The techniques presented can be useful in studying both typical and atypical motor control, and can be modified to investigate a broad range of tasks and scientific questions.

Monitoring brain activity during upright motor tasks is of great value when investigating the neural source of movement disorders. Here, we demonstrate a protocol that combines functional near infrared spectroscopy with continuous monitoring of muscle and kinematic activity during 4 types of motor tasks.

Funcional Espectroscopia de Infrarrojo Cercano de las Regiones sensoriales y motoras del cerebro con simultánea cinemática y EMG Supervisión Durante las tareas motoras

There are several advantages that functional near-infrared spectroscopy (fNIRS) presents in the study of the neural control of human movement. It is ...

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.

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

Adquisición de una alta precisión Skilled Miembro Anterior Alcanzar Tarea en Ratas

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

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be time-intensive and ambiguous to quantify beyond simple success rates. Here, we describe the training procedure for reach-and-pull tasks with ETH Pattus, a robotic platform for automated forelimb reaching training that records pulling and hand rotation movements in rats. Kinematic quantification of the performed pulling attempts reveals the presence of distinct temporal profiles of movement parameters such as pulling velocity, spatial variability of the pulling trajectory, deviation from midline, as well as pulling success. We show how minor adjustments in the training paradigm result in alterations in these parameters, revealing their relation to task difficulty, general motor function or skilled task execution. Combined with electrophysiological, pharmacological and optogenetic techniques, this paradigm can be used to explore the mechanisms underlying motor learning and memory formation, as well as loss and recovery of function (e.g. after stroke).

A paradigm is presented for training and analysis of an automated skilled reaching task in rats. Analysis of pulling attempts reveals distinct subprocesses of motor learning.

La investigación de los procesos de aprendizaje de habilidades motoras con una robótica Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be ...

Using a Split-belt Treadmill to Evaluate Generalization of Human Locomotor Adaptation

Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. However, studying human locomotor learning can be challenging. During infancy and childhood, the neuromuscular system is quite immature, and it is unlikely that locomotor learning during early stages of development is governed by the same mechanisms as in adulthood. By the time humans reach maturity, they are so proficient at walking that it is difficult to come up with a sufficiently novel task to study de novo locomotor learning. The split-belt treadmill, which has two belts that can drive each leg at a different speed, enables the study of both short- (i.e., immediate) and long-term (i.e., over minutes-days; a form of motor learning) gait modifications in response to a novel change in the walking environment. Individuals can easily be screened for previous exposure to the split-belt treadmill, thus ensuring that all experimental participants have no (or equivalent) prior experience. This paper describes a typical split-belt treadmill adaptation protocol that incorporates testing methods to quantify locomotor learning and generalization of this learning to other walking contexts. A discussion of important considerations for designing split-belt treadmill experiments follows, including factors like treadmill belt speeds, rest breaks, and distractors. Additionally, potential but understudied confounding variables (e.g., arm movements, prior experience) are considered in the discussion.

We describe a protocol for investigating human locomotor adaptation using the split-belt treadmill, which has two belts that can drive each leg at a different speed. We specifically focus on a paradigm designed to test the generalization of adapted locomotor patterns to different walking contexts (e.g., gait speeds, walking environments).

Con una cinta de cinturón de Split para evaluar la generalización de la adaptación humana Aparato Locomotor

Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. ...

Novel Object Recognition Test for the Investigation of Learning and Memory in Mice

The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is fairly simple and can be completed over 3 days: habituation day, training day, and testing day. During training, the mouse is allowed to explore 2 identical objects. On test day, one of the training objects is replaced with a novel object. Because mice have an innate preference for novelty, if the mouse recognizes the familiar object, it will spend most of its time at the novel object. Due to this innate preference, there is no need for positive or negative reinforcement or long training schedules. Additionally, the ORT can also be modified for numerous applications. The retention interval can be shortened to examine short-term memory, or lengthened to probe long-term memory. Pharmacological intervention can be used at various times prior to training, after training, or prior to recall to investigate different phases of learning (i.e., acquisition, early or late consolidation, or recall). Overall, the ORT is a relatively low-stress, efficient test for memory in mice, and is appropriate for the detection of neuropsychological changes following pharmacological, biological, or genetic manipulations.

The object recognition test (ORT) is a simple and efficient assay for evaluating learning and memory in mice. The methodology is described below.

Prueba de reconocimiento de objeto novedoso para la investigación del aprendizaje y la memoria en ratones

The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is ...

Using Virtual Reality to Transfer Motor Skill Knowledge from One Hand to Another

As far as acquiring motor skills is concerned, training by voluntary physical movement is superior to all other forms of training (e.g. training by observation or passive movement of trainee&#39;s hands by a robotic device). This obviously presents a major challenge in the rehabilitation of a paretic limb since voluntary control of physical movement is limited. Here, we describe a novel training scheme we have developed that has the potential to circumvent this major challenge. We exploited the voluntary control of one hand and provided real-time movement-based manipulated sensory feedback as if the other hand is moving. Visual manipulation through virtual reality (VR) was combined with a device that yokes left-hand fingers to passively follow right-hand voluntary finger movements. In healthy subjects, we demonstrate enhanced within-session performance gains of a limb in the absence of voluntary physical training. Results in healthy subjects suggest that training with the unique VR setup might also be beneficial for patients with upper limb hemiparesis by exploiting the voluntary control of their healthy hand to improve rehabilitation of their affected hand.

We describe a novel virtual-reality based setup which exploits voluntary control of one hand to improve motor-skill performance in the other (non-trained) hand. This is achieved by providing real-time movement-based sensory feedback as if the non-trained hand is moving. This new approach may be used to enhance rehabilitation of patients with unilateral hemiparesis.

Uso de realidad Virtual para transferir Motor habilidad conocimiento de un lado a otro

As far as acquiring motor skills is concerned, training by voluntary physical movement is superior to all other forms of training (e.g. training by ...

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 ...