Los autores desean agradecer al Prof. ME Schwab, el Dr. P. Freund, Dr. A. Wyss, el Dr. S. Bashir, el Dr. A. Mir, el Dr. J. Bloch, Dr. JF Brunet, el Dr. J. Aebischer, el Dr. A. Meszaros, el Dr. V. Goetschman por su contribución a los experimentos y análisis previos. Los montajes experimentales fueron construidos por André Gaillard, Bernard Aebischer y Monney Laurent. En las instalaciones de animales, los monos fueron colocados bajo la supervisión de los cuidadores profesionales: Josef Corpataux, Laurent Bossy y Jacques Maillard. Las pruebas de comportamiento y análisis de los datos, así como la histología, se llevaron a cabo con las aportaciones de gran valor de los técnicos de laboratorio: Véronique Moret (también web master), Tinguely Françoise, Roulin Christine, Bennefeld Monica, Martí y Christiane Fischer Georgette. Este trabajo fue apoyado por la Fundación Nacional Suiza para la Ciencia, las subvenciones no 31-61857.00, 310000-110005, 31003A-132465 (EMR), 310030-118357, 31003A-104061 (TW), 310030-120411 (ABS), PZ00P3_121646 (ES), Fundación Novartis, el Centro Nacional de Competencia en Investigación (NCCR) sobre &quot;La plasticidad neuronal y la reparación&quot;.

<ol>
	<li>Lemon, R. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Descending+pathways+in+motor+control.">Descending pathways in motor control.</a> Annu. Rev. Neurosci. 31, 195-218 (2008).</li><li>Courtine, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Can+experiments+in+nonhuman+primates+expedite+the+translation+of+treatments+for+spinal+cord+injury+in+humans?.">Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?.</a> Nat. Med. 13, 561-566 (2007).</li><li>Capitanio, J. P., Emborg, 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=Contributions+of+non-human+primates+to+neuroscience+research.">Contributions of non-human primates to neuroscience research.</a> Lancet. 371, 1126-1135 (2008).</li><li>Brinkman, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Supplementary+motor+area+of+the+monkey's+cerebral+cortex:+short-+and+long-term+deficits+after+unilateral+ablation+and+the+effects+of+subsequent+callosal+section.">Supplementary motor area of the monkey's cerebral cortex: short- and long-term deficits after unilateral ablation and the effects of subsequent callosal section.</a> J. Neurosci. 4, 918-929 (1984).</li><li>Brinkman, J., Kuypers, H. 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Res. 14, 268-280 (1997).</li><li>Kermadi, I., Liu, Y., Tempini, A., Calciati, E., Rouiller, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuronal+activity+in+the+primate+supplementary+motor+area+and+the+primary+motor+cortex+in+relation+to+spatio-temporal+bimanual+coordination.">Neuronal activity in the primate supplementary motor area and the primary motor cortex in relation to spatio-temporal bimanual coordination.</a> Somatosens. Mot. Res. 15, 287-308 (1998).</li><li>Kermadi, I., Liu, Y., Rouiller, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Do+bimanual+motor+actions+involve+the+dorsal+premotor+(PMd),+cingulate+(CMA)+and+posterior+parietal+(PPC)+cortices?+Comparison+with+primary+and+supplementary+motor+cortical+areas.">Do bimanual motor actions involve the dorsal premotor (PMd), cingulate (CMA) and posterior parietal (PPC) cortices? Comparison with primary and supplementary motor cortical areas.</a> Somatosensory and Motor Research. 17, 255-271 (2000).</li><li>Wannier, T., Liu, J., Morel, A., Jouffrais, C., Rouiller, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuronal+activity+in+primate+striatum+and+pallidum+related+to+bimanual+motor+actions.">Neuronal activity in primate striatum and pallidum related to bimanual motor actions.</a> NeuroReport. 13, 143-147 (2002).</li><li>Rouiller, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dexterity+in+adult+monkeys+following+early+lesion+of+the+motor+cortical+hand+area:+the+role+of+cortex+adjacent+to+the+lesion.">Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion.</a> Eur. J. Neurosci. 10, 729-740 (1998).</li><li>Liu, Y., Rouiller, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+recovery+of+dexterity+following+unilateral+lesion+of+the+sensorimotor+cortex+in+adult+monkeys.">Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys.</a> Exp. Brain. Res. 128, 149-159 (1999).</li><li>Freund, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nogo-A-specific+antibody+treatment+enhances+sprouting+and+functional+recovery+after+cervical+lesion+in+adult+primates.">Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates.</a> Nature. Med. 12, 790-792 (2006).</li><li>Freund, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anti-Nogo-A+antibody+treatment+promotes+recovery+of+manual+dexterity+after+unilateral+cervical+lesion+in+adult+primates--re-examination+and+extension+of+behavioral+data.">Anti-Nogo-A antibody treatment promotes recovery of manual dexterity after unilateral cervical lesion in adult primates--re-examination and extension of behavioral data.</a> Eur. J. Neurosci. 29, 983-996 (2009).</li><li>Kaeser, M. <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+Unilateral+Motor+Cortex+Lesion+on+Ipsilesional+Hand's+Reach+and+Grasp+Performance+in+Monkeys:+Relationship+With+Recovery+in+the+Contralesional+Hand.">Effects of Unilateral Motor Cortex Lesion on Ipsilesional Hand's Reach and Grasp Performance in Monkeys: Relationship With Recovery in the Contralesional Hand.</a> J. Neurophysiol. 103, 1603-1645 (2010).</li><li>Kaeser, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autologous+adult+cortical+cell+transplantation+enhances+functional+recovery+following+unilateral+lesion+of+motor+cortex+in+primates:+a+pilot+study.">Autologous adult cortical cell transplantation enhances functional recovery following unilateral lesion of motor cortex in primates: a pilot study.</a> Neurosurgery. 68, 1405-1417 (2011).</li><li>Bashir, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Short-term+effects+of+unilateral+lesion+of+the+primary+motor+cortex+(M1)+on+Ipsilesional+hand+dexterity+in+adult+macaque+monkeys.">Short-term effects of unilateral lesion of the primary motor cortex (M1) on Ipsilesional hand dexterity in adult macaque monkeys.</a> Brain Structure and Function. , (2011).</li><li>Hamadjida, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+anti-Nogo-A+treatment+on+the+reorganization+of+callosal+connectivity+of+the+premotor+cortical+areas+following+unilateral+lesion+of+primary+motor+cortex+(M1)+in+adult+macaque+monkeys.">Influence of anti-Nogo-A treatment on the reorganization of callosal connectivity of the premotor cortical areas following unilateral lesion of primary motor cortex (M1) in adult macaque monkeys.</a> , (2011).</li><li>Jenny, A. B., Inukai, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Principles+of+motor+organization+of+the+monkey+cervical+spinal+cord.">Principles of motor organization of the monkey cervical spinal cord.</a> J. Neurosci. 3, 567-575 (1983).</li><li>Schmidlin, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progressive+plastic+changes+in+the+hand+representation+of+the+primary+motor+cortex+parallel+incomplete+recovery+from+a+unilateral+section+of+the+corticospinal+tract+at+cervical+level+in+monkeys.">Progressive plastic changes in the hand representation of the primary motor cortex parallel incomplete recovery from a unilateral section of the corticospinal tract at cervical level in monkeys.</a> Brain Research. 1017, 172-183 (2004).</li><li>Schmidlin, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+of+the+hand+representation+in+the+ipsilateral+primary+motor+cortex+following+unilateral+section+of+the+corticospinal+tract+at+cervical+level+in+monkeys.">Reduction of the hand representation in the ipsilateral primary motor cortex following unilateral section of the corticospinal tract at cervical level in monkeys.</a> BMC Neuroscience. 6, 56-56 (2005).</li><li>Prescott, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Refinement+of+the+use+of+food+and+fluid+control+as+motivational+tools+for+macaques+used+in+behavioural+neuroscience+research:+report+of+a+Working+Group+of+the+NC3Rs.">Refinement of the use of food and fluid control as motivational tools for macaques used in behavioural neuroscience research: report of a Working Group of the NC3Rs.</a> J. Neurosci. Methods. 193, 167-188 (2010).</li><li>Darling, W. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+effects+of+motor+cortex+injury+on+recovery+of+dexterous+movements.">Volumetric effects of motor cortex injury on recovery of dexterous movements.</a> Exp. Neurol. 220, 90-108 (2009).</li><li>Darling, W. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Minimal+forced+use+without+constraint+stimulates+spontaneous+use+of+the+impaired+upper+extremity+following+motor+cortex+injury.">Minimal forced use without constraint stimulates spontaneous use of the impaired upper extremity following motor cortex injury.</a> Exp. Brain. Res. 202, 529-542 (2010).</li><li>McNeal, D. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+long-term+reorganization+of+the+corticospinal+projection+from+the+supplementary+motor+cortex+following+recovery+from+lateral+motor+cortex+injury.">Selective long-term reorganization of the corticospinal projection from the supplementary motor cortex following recovery from lateral motor cortex injury.</a> J. Comp. Neurol. 518, 586-621 (2010).</li><li>Nishimura, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time-dependent+central+compensatory+mechanisms+of+finger+dexterity+after+spinal+cord+injury.">Time-dependent central compensatory mechanisms of finger dexterity after spinal cord injury.</a> Science. 318, 1150-1155 (2007).</li><li>Pizzimenti, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+reaching+kinematics+and+prehensile+dexterity+in+nonhuman+primates.">Measurement of reaching kinematics and prehensile dexterity in nonhuman primates.</a> J. Neurophysiol. 98, 1015-1029 (2007).</li></ol>

No hay conflictos de interés declarado.

Aunque las tareas actuales de comportamiento se han considerado hasta ahora en nuestro laboratorio en el contexto de los estudios relacionados con la lesión de la médula cervical o lesión de la corteza motora, con el objetivo de probar varios tratamientos (ver 14,15,17 y <a href="http://www.unifr.ch/neuro/rouiller">http:/ / www.unifr.ch / neuro / Rouiller</a> &gt; seleccione &quot;investigación&quot; en la barra de menú superior, luego&gt; &quot;motor del sistema&quot;&gt; &quot;la recuperación después de la lesión&quot;), también pueden tener una aplicación más amplia, como la destreza manual es también un aspecto a tener en cuenta otras patologías, como la enfermedad de Parkinson (monos MPTP) o en el caso de la información sensorial de-afferentation propiocepción que afectan y / o el sentido del tacto (en especial la prueba de 2 en ausencia de un control visual). Las pruebas de comportamiento que aquí se propone es adecuada para investigar el control motor de los movimientos distal de la extremidad anterior, como implicados en la destreza manual. La especificidad de las pruebas se demuestra porla ausencia de déficit (a excepción de un par de días) en caso de una lesión y que no altere los componentes pertinentes del sistema de control: en efecto, en el caso de una lesión colocado más caudal de las neuronas motoras que controlan los músculos mano, no había déficit. La pertinencia de la prueba 1 se puede apreciar al comparar las secuencias de vídeo tomadas en dos momentos de la curva de recuperación después de la lesión, que se diferencian por una mejora de la recuperación funcional del 25%, posiblemente en relación con un tratamiento de terapia celular 17. A pesar de una fase inicial, de formación relativamente corto al principio (que dura generalmente 2-3 meses), las pruebas de comportamiento que aquí se propone es relativamente &quot;natural&quot; y directo, en comparación con los complejos (por ejemplo, condicional) tareas para las que la formación de los monos puede tomar cerca de un año o más. El refuerzo positivo se basa en alimentos sólidos, que es menos sensible en el punto de vista ético de la privación de agua, por lo general se utiliza en más comcomplejas tareas 23. No hay necesidad de privar a los monos de los alimentos para obtener resultados estables y consistentes. Los pellets recibidos durante las tareas de representar el primer acceso a la comida en el día de la sesión de comportamiento (si se asume que el mono no se come en la noche anterior, sin embargo los alimentos se expedirá hasta el final de la tarde del día anterior) . Es fundamental que cada mono lleva a cabo la sesión de la conducta, al mismo tiempo de la jornada, así como respetando el mismo orden secuencial entre los monos diferentes que forman un grupo en la sala de la vivienda. Como los monos son sensibles a los acontecimientos externos perturbadores, las tareas de comportamiento debe ser llevado a cabo en presencia de la música de fondo, enmascarando el ruido potencial perturbador procedentes de habitaciones contiguas o laboratorios. Es fundamental que durante toda la duración del experimento (desde la formación inicial hasta la última sesión experimental diaria, un período de varios meses o incluso años), un mono dado espuesto al día, bajo la supervisión del investigador mismo. Las pruebas actuales de comportamiento, que se utiliza desde hace varios años en nuestro laboratorio para cuantificar la destreza manual, son hasta cierto punto comparable a otras pruebas de destreza manual recientemente reportados en la literatura 24-28. Sin embargo, existe una imperiosa necesidad de estandarizar las pruebas entre laboratorios diferentes (para una mejor comparación), que es un objetivo provisional del presente informe. En la demanda, las propiedades detalladas de los montajes se muestra aquí para las pruebas de 1-4 puede ser proporcionada por el autor correspondiente, con el fin de replicar. Más allá del tema de la medicina regenerativa (la recuperación de la lesión de la médula espinal o de la corteza cerebral), la paleta actual de las pruebas pueden ser adecuados para hacer frente en condiciones normales no humanos primates temas de desarrollo (por ejemplo, por supuesto el tiempo de desarrollo motor de los movimientos diestros), para investigar aspectos lateralización (lado preferencia / dominio) y a las preguntas descifrar la evolución de cOMPARACIÓN las habilidades motoras de las diferentes especies de primates, incluyendo seres humanos. Note sin embargo que las dimensiones de los aparatos deben adaptarse en función del tamaño de los dígitos (grosor y longitud) de las especies de primates, ya que puede influir en la ejecución de tareas. En el presente estudio, las pruebas se llevaron a cabo en monos macaca fascicularis, que van desde 2,5 a 8 años de edad y un peso de entre 2,5 y 8 kg. La longitud del dedo índice (utilizado por primera vez de manipular las pastillas) oscila entre 32 y 35 mm, mientras que la circunferencia de la falange distal (punta) del dedo índice entre 22 y 25 mm en los monos incluidos en nuestros estudios. Como prueba en los experimentos anteriores, las mismas pruebas son adecuadas para captar macaca mulatta también. Todos los experimentos se realizaron de conformidad con la Guía para el Cuidado y Uso de Animales de Laboratorio (1996) y aprobado por el local (Suiza) las autoridades veterinarias. Todos los procedimientos experimentales en el monos, así como las condiciones de detención en las instalaciones de animales, se describen en detalle en los informes recientes de nuestro laboratorio: véanse las referencias 12-18.

behavioral assessment of manual dexterity in non-human primates

El corticoespinal (CS) es el aparato de apoyo anatómica de la capacidad del motor exquisita habilidad para manipular objetos pequeños, sobre todo una prerrogativa de los primates 1. En caso de lesión que afecta el sistema de proyección CS en su origen (la lesión de las áreas motoras corticales) oa lo largo de su trayectoria (lesión de la médula cervical), hay una dramática pérdida de destreza manual (parálisis de la mano), como se observa en algunos pacientes tetrapléjicos o hemipléjicos . Aunque hay una cierta recuperación funcional después de la lesión espontánea tal, sigue siendo muy limitado en el adulto. Diversas estrategias terapéuticas actualmente propuestas (por ejemplo, la terapia celular, la neutralización de moléculas inhibidoras del crecimiento axonal, la aplicación de factores de crecimiento, etc), que son en su mayoría desarrollados en los roedores. Sin embargo, antes de la aplicación clínica, se recomienda a menudo para comprobar la viabilidad, la eficacia y seguridad del tratamiento en los primates no humanos. Esto es especialmente cierto cuando el objetivo es restaurar la destreza manual después deuna lesión del sistema nervioso central, como la organización del sistema de motor de los roedores es diferente de la de los primates 1,2. Los monos macacos se muestran aquí como un modelo adecuado de comportamiento para cuantificar la destreza manual de los primates, para reflejar el déficit resultante de la lesión de la corteza motora o de la médula cervical, por ejemplo, medir el grado de recuperación funcional espontánea y, cuando se aplique un tratamiento, evaluar lo mucho que puede mejorar la recuperación funcional. La evaluación del comportamiento de la destreza manual se basa en cuatro distintas, tareas complementarias, alcanzar y agarrar manual (uso de agarre de precisión para captar pellets), lo que requiere una formación inicial de los monos macacos adultos. La preparación de los animales se ha demostrado, así como el posicionamiento con respecto a la conducta puesta en marcha. El rendimiento de un mono típico se ilustra para cada tarea. La recogida y el análisis de los parámetros correspondientes que manipula la mano precisación, así como el control de la fuerza, se explica y se demuestra con resultados representativos. Estos datos se colocan luego en un contexto más amplio, que muestra cómo los datos de comportamiento puede ser explotado para investigar el impacto de una lesión de la médula espinal o de una lesión de la corteza motora y en qué medida un tratamiento puede mejorar la recuperación funcional espontánea, la comparación por los diferentes grupos de monos (los tratados frente a sham tratados, por ejemplo). Ventajas y limitaciones de las pruebas de comportamiento se discuten. El enfoque del comportamiento actual está en línea con informes anteriores, haciendo hincapié en la pertinencia del modelo de primates no humanos en el contexto de las enfermedades del sistema nervioso 2,3.

Watch this Scientific Journal Video about Behavioral Assessment of Manual Dexterity in Non-Human Primates at JoVE.com

Behavioral Assessment of Manual Dexterity in Non-Human Primates

Como la destreza manual es una prerrogativa de los primates, principalmente, tareas conductuales se han desarrollado en los monos macacos. Cuatro alcanzar y agarrar las tareas de comprensión, que mide la capacidad de manipulación de la mano y la fuerza, permiten establecer la recuperación funcional después de una lesión del sistema nervioso central y para evaluar el efecto de un tratamiento.

Evaluación del Comportamiento de la destreza manual en primates no humanos

The corticospinal (CS) tract is the anatomical support of the exquisite motor ability to skillfully manipulate small objects, a prerogative mainly of ...

behavioral-assessment-of-manual-dexterity-in-non-human-primates

Research

JoVE Journal

Neuroscience

22.2K vistas.  University of Fribourg. Como la destreza manual es una prerrogativa de los primates, principalmente, tareas conductuales se han desarrollado en los monos macacos. Cuatro alcanzar y agarrar las tareas de comprensión, que mide la capacidad de manipulación de la mano y la fuerza, permiten establecer la recuperación funcional después de una lesión del sistema nervioso central y para evaluar el efecto de un tratamiento.

Video: Behavioral Assessment of Manual Dexterity in Non-Human Primates

Combining Behavioral Endocrinology and Experimental Economics: Testosterone and Social Decision Making

Behavioral endocrinological research in humans as well as in animals suggests that testosterone plays a key role in social interactions. Studies in rodents have shown a direct link between testosterone and aggressive behavior1 and folk wisdom adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic or even aggressive behavior2. However, many researchers doubt a direct testosterone-aggression link in humans, arguing instead that testosterone is primarily involved in status-related behavior3,4. As a high status can also be achieved by aggressive and antisocial means it can be difficult to distinguish between anti-social and status seeking behavior.
We therefore set up an experimental environment, in which status can only be achieved by prosocial means. In a double-blind and placebo-controlled experiment, we administered a single sublingual dose of 0.5 mg of testosterone (with a hydroxypropyl-&beta;-cyclodextrin carrier) to 121 women and investigated their social interaction behavior in an economic bargaining paradigm. Real monetary incentives are at stake in this paradigm; every player A receives a certain amount of money and has to make an offer to another player B on how to share the money. If B accepts, she gets what was offered and player A keeps the rest. If B refuses the offer, nobody gets anything. A status seeking player A is expected to avoid being rejected by behaving in a prosocial way, i.e. by making higher offers.
The results show that if expectations about the hormone are controlled for, testosterone administration leads to a significant increase in fair bargaining offers compared to placebo. The role of expectations is reflected in the fact that subjects who report that they believe to have received testosterone make lower offers than those who say they believe that they were treated with a placebo. These findings suggest that the experimental economics approach is sensitive for detecting neurobiological effects as subtle as those achieved by administration of hormones. Moreover, the findings point towards the importance of both psychosocial as well as neuroendocrine factors in determining the influence of testosterone on human social behavior.

The procedure described in this protocol shows that testosterone administration and folk beliefs about testosterone may be associated with directly opposed social behaviors.

La combinación del comportamiento de Endocrinología Experimental y Economía: Decisión de la testosterona y sociales que

Behavioral endocrinological research in humans as well as in animals suggests that testosterone plays a key role in social interactions. Studies in ...

Investigación

Neurociencias

A General Method for Evaluating Incubation of Sucrose Craving in Rats

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking 1. Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food 2-4.
As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats self-administer either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties 5. This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs.
In the past decade, we have focused on how the length of time following reward self-administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced-abstinence. This "incubation of craving" is observed in rats that have self-administered either food or drugs of abuse 4,6. This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors.
Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrose-paired cue following extinction of lever pressing within the sucrose self-administration context (Extinction without cues) or as responding for sucrose-paired cues in a general extinction context (Extinction with cues).

Responding for food or drug-paired cues increases over the course of a period of abstinence and this may relate to an increased susceptibility to relapse behaviors. Here we detail a procedure for evaluating this "incubation of craving" in rats that have self-administered sucrose.

Un método general para la evaluación de incubación de sacarosa en ratas Deseo

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and ...

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day1-5. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT).
Although circadian rhythms in running-wheel activity are typically linked to the SCN clock6-8, circadian oscillators in many other regions of the brain and body9-14 could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN15,16 and instead, are correlated with changes in the activity of extra-SCN oscillators17-20. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.

Circadian rhythms in voluntary wheel-running activity in mammals are tightly coupled to the molecular oscillations of a master clock in the brain. As such, these daily rhythms in behavior can be used to study the influence of genetic, pharmacological, and environmental factors on the functioning of this circadian clock.

Registro y análisis de los ritmos circadianos en funcionamiento las ruedas Actividad en roedores

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day1-5. Nocturnal rodents, ...

Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity and extent of dendritic arborization correlates well with the synaptic plasticity in these cells. A reliable method for assessment of dendritic arborization is needed to characterize the deleterious effects of neurological disorders on these structures and to determine the effects of therapeutic interventions. However, quantification of these structures has proven to be a formidable task given their complex and dynamic nature. Fortunately, sophisticated imaging techniques can be paired with conventional staining methods to assess the state of dendritic arborization, providing a more reliable and expeditious means of assessment. Below is an example of how these imaging techniques were paired with staining methods to characterize the dendritic arborization in wild type mice. These complementary imaging methods can be used to qualitatively and quantitatively assess dendritic arborization that span a rather wide area within the hippocampal region.

We describe two methods for visualization and quantification of dendritic arborization in the hippocampus of mouse models: real-time and extended depth of field imaging. While the former method allows sophisticated topographical tracing and quantification of the extent of branching, the latter allows speedy visualization of the dendritic tree.

Evaluación de la arborización dendrítica en el giro dentado de la región del hipocampo en ratones

Dendritic arborization has been shown to be a reliable marker for examination of structural and functional integrity of neurons. Indeed, the complexity ...

Quantification of Filamentous Actin (F-actin) Puncta in Rat Cortical Neurons

Filamentous actin protein (F-actin) plays a major role in spinogenesis, synaptic plasticity, and synaptic stability. Changes in dendritic F-actin rich structures suggest alterations in synaptic integrity and connectivity. Here we provide a detailed protocol for culturing primary rat cortical neurons, Phalloidin staining for F-actin puncta, and subsequent quantification techniques. First, the frontal cortex of E18 rat embryos are dissociated into low-density cell culture, then the neurons grown in vitro for at least 12-14 days. Following experimental treatment, the cortical neurons are stained with AlexaFluor 488 Phalloidin (to label the dendritic F-actin puncta) and microtubule-associated protein 2 (MAP2; to validate the neuronal cells and dendritic integrity). Finally, specialized software is used to analyze and quantify randomly selected neuronal dendrites. F-actin rich structures are identified on second order dendritic branches (length range 25-75 &#181;m) with continuous MAP2 immunofluorescence. The protocol presented here will be a useful method for investigating changes in dendritic synapse structures subsequent to experimental treatments.

Quantification of Filamentous Actin F-actin Puncta in Rat Cortical Neurons

Filamentous actin (F-actin) plays an important role in spinogenesis, synaptic plasticity, and synaptic stability. Quantification of F-actin puncta is therefore a useful tool to study the integrity of synaptic structures. This protocol describes the procedures of quantifying F-actin puncta labeled with Phalloidin in low-density primary cortical neuronal cultures.

La cuantificación de la actina filamentosa (F-actina) puntos lagrimales en las neuronas corticales de rata

Filamentous actin protein (F-actin) plays a major role in spinogenesis, synaptic plasticity, and synaptic stability. Changes in dendritic F-actin rich ...

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology

In the central nervous system, the D1-alpha subtype receptor (Drd1&#945;) is the most abundant dopamine (DA) receptor, which plays a vital role in regulating neuronal growth and development. However, the mechanisms underlying Drd1&#945; receptor abnormalities mediating behavioral responses and modulating working memory function are still unclear. Using a novel RNA in situ hybridization assay, the current study identified dopamine Drd1&#945; receptor and tyrosine hydroxylase (TH) RNA expression from DA-related circuitry in the nucleus accumbens (NAc) area and substantia nigra region (SNR), respectively. Drd1&#945; expression in the NAc shows a &#34;discrete dot&#34; staining pattern. Clear sex differences in Drd1&#945; expression were observed. In contrast, TH shows a &#34;clustered&#34; staining pattern. Regarding TH expression, female rats displayed a higher signal expression per cell relative to male animals. The methods presented here provide a novel in situ hybridization technique for investigating changes in dopamine system dysfunction during the progression of central nervous system diseases.

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology

Identification of dopamine D1-alpha receptor in the nucleus accumbens is critical for clarifying D1 receptor dysfunction during a central nervous system disease. We performed a novel RNA in situ hybridization assay to visualize single RNA molecules in a specific brain area.

Identificación del Receptor de dopamina D1-alfa en roedores núcleo Accumbens por una innovador ARN In Situ la tecnología de detección

In the central nervous system, the D1-alpha subtype receptor (Drd1&#945;) is the most abundant dopamine (DA) receptor, which plays a vital role in ...

The Power of Interstimulus Interval for the Assessment of Temporal Processing in Rodents

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in neurocognitive disorders. Despite the popularization of prepulse inhibition (PPI) in recent years, many current protocols promote using a percent of control measure, thereby precluding the assessment of temporal processing. The present study used cross-modal PPI and gap prepulse inhibition (gap-PPI) to demonstrate the benefits of employing a range of interstimulus intervals (ISIs) to delineate effects of sensory modality, psychostimulant exposure, and age. Assessment of sensory modality, psychostimulant exposure, and age reveals the utility of an approach varying the interstimulus interval (ISI) to establish the shape of the ISI function, including increases (sharper curve inflections) or decreases (flattening of the response amplitude curve) in startle amplitude. Additionally, shifts in peak response inhibition, suggestive of a differential sensitivity to the manipulation of ISI, are often revealed. Thus, the systematic manipulation of ISI affords a critical opportunity to evaluate temporal processing, which may reveal the underlying neural mechanisms involved in neurocognitive disorders.

Temporal processing, a preattentive process, may underlie deficits in higher-level cognitive processes, including attention, commonly observed in neurocognitive disorders. Using prepulse inhibition as an exemplar paradigm, we present a protocol for manipulating interstimulus interval (ISI) to establish the shape of the ISI function to provide an assessment of temporal processing.

El poder del Interstimulus intervalo para la evaluación de proceso Temporal en roedores

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in ...

Assessment of Long-term Depression Induction in Adult Cerebellar Slices

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from parallel fibers (PF) to Purkinje cells (PC) is considered the basis for motor learning, and deficiencies of both LTD and motor learning are observed in various gene-manipulated animals. Common motor learning sets, such as adaptation of the optokinetic reflex (OKR), the vestibular-ocular reflex (VOR), and rotarod test were used for evaluation of motor learning ability. However, results obtained from the GluA2-carboxy terminus modified knock-in mice demonstrated normal adaptation of the VOR and the OKR, despite lacking PF-LTD. In that report, induction of LTD was only attempted using one type of stimulation protocol at room temperature. Thus, conditions to induce cerebellar LTD were explored in the same knock-in mutants using various protocols at near physiological temperature. Finally, we found stimulation protocols, by which LTD could be induced in these gene-manipulated mice. In this study, a set of protocols are proposed to evaluate LTD-induction, which will more accurately allow examination of the causal relationship between LTD and motor learning. In conclusion, experimental conditions are crucial when evaluating LTD in gene-manipulated mice.

In some gene-manipulated animals, using a single protocol may fail to induce LTD in cerebellar Purkinje cells, and there may be a discrepancy between LTD and motor learning. Multiple protocols are necessary to assess LTD-induction in gene-manipulated animals. Standard protocols are shown.

Evaluación de la inducción a largo plazo de la depresión en rodajas de cerebelosores adultos

Synaptic plasticity provides a mechanism for learning and memory. For cerebellar motor learning, long-term depression (LTD) of synaptic transmissions from ...

Ballistic Labeling of Pyramidal Neurons in Brain Slices and in Primary Cell Culture

It has been reported that the size and shape of dendritic spines is related to their structural plasticity. To identify the morphological structure of pyramidal neurons and dendritic spines, a ballistic labeling technique can be utilized. In the present protocol, pyramidal neurons are labeled with DilC18(3) dye and analyzed using neuronal reconstruction software to assess neuronal morphology and dendritic spines. To investigate neuronal structure, dendritic branching analysis and Sholl analysis are performed, allowing researchers to draw inferences about dendritic branching complexity and neuronal arbor complexity, respectively. The evaluation of dendritic spines is conducted using an automatic assisted classification algorithm integral to the reconstruction software, which classifies spines into four categories (i.e., thin, mushroom, stubby, filopodia). Furthermore, an additional three parameters (i.e., length, head diameter, and volume) are also chosen to assess alterations in dendritic spine morphology. To validate the potential of wide application of the ballistic labeling technique, pyramidal neurons from in vitro cell culture were successfully labeled. Overall, the ballistic labeling method is unique and useful for visualizing neurons in different brain regions in rats, which in combination with sophisticated reconstruction software, allows researchers to elucidate the possible mechanisms underlying neurocognitive dysfunction.

We present a protocol to label and analyze pyramidal neurons, which is critical for evaluating potential morphological alterations in neurons and dendritic spines that may underlie neurochemical and behavioral abnormalities.

Etiquetado balístico de las neuronas piramidales en las rebanadas cerebrales y en el cultivo celular primario

It has been reported that the size and shape of dendritic spines is related to their structural plasticity. To identify the morphological structure of ...

A Rat Model of EcoHIV Brain Infection

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV). First, the lentiviral construct of EcoHIV was packaged in cultured 293 FT cells for 48 hours. Then, the conditional medium was concentrated and titered. Next, we performed bilateral stereotaxic injections of the EcoHIV-EGFP into F344/N rat brain tissue. One week after infection, EGFP fluorescence signals were detected in the infected brain tissue, indicating that EcoHIV successfully induces an active HIV infection in rats. In addition, immunostaining for the microglial cell marker, Iba1, was performed. The results indicated that microglia were the predominant cell type harboring EcoHIV. Furthermore, EcoHIV rats exhibited alterations in temporal processing, a potential underlying neurobehavioral mechanism of HAND as well as synaptic dysfunction eight weeks after infection. Collectively, the present study extends the EcoHIV model of HIV-1 infection to the rat offering a valuable biological system to study HIV-1 viral reservoirs in the brain as well as HAND and associated comorbidities such as drug abuse.

Here, we present a protocol to establish a new rat model of active HIV infection using chimeric HIV (EcoHIV), which is critical for enhancing our understanding of HIV-1 viral reservoirs in the brain and offering a system to study HIV-associated neurocognitive disorders and associated comorbidities (i.e., drug abuse).

Un modelo de rata de la infección cerebral EcoHIV

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. ...