El financiamiento para esta investigación fue proporcionado por los pasos de Garnett y Rodney Williams Memorial Foundation y la Universidad La Trobe.

<ol>
	<li>Mauger, S. J., Shivdasani, M. N., Rathbone, G. D., Argent, R. E., Paolini, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+in+vivo+investigation+of+first+spike+latencies+in+the+inferior+colliculus+in+response+to+multichannel+penetrating+auditory+brainstem+implant+stimulation.">An in vivo investigation of first spike latencies in the inferior colliculus in response to multichannel penetrating auditory brainstem implant stimulation.</a> Journal of Neural Engineering. 7, 036004-036004 (2010).</li><li>Shivdasani, M. N., Mauger, S. J., Argent, R. E., Rathbone, G. D., Paolini, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inferior+colliculus+responses+to+dual-site+intralamina+stimulation+in+the+ventral+cochlear+nucleus.">Inferior colliculus responses to dual-site intralamina stimulation in the ventral cochlear nucleus.</a> J. Comp. Neurol. 518, 4226-4242 (2010).</li><li>Shivdasani, M. N., Mauger, S. J., Rathbone, G. D., Paolini, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inferior+colliculus+responses+to+multichannel+microstimulation+of+the+ventral+cochlear+nucleus:+Implications+for+auditory+brain+stem+implants.">Inferior colliculus responses to multichannel microstimulation of the ventral cochlear nucleus: Implications for auditory brain stem implants.</a> Journal of Neurophysiology. 99, 1-13 (2007).</li><li>Lenarz, M., Lim, H. H., Patrick, J. F., Anderson, D. J., Lenarz, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrophysiological+Validation+of+a+Human+Prototype+Auditory+Midbrain+Implant+in+a+Guinea+Pig+Model.">Electrophysiological Validation of a Human Prototype Auditory Midbrain Implant in a Guinea Pig Model.</a> JARO. 7, 383-398 (2006).</li><li>Lim, H. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auditory+Cortical+Responses+to+Electrical+Stimulation+of+the+Inferior+Colliculus:+Implications+for+an+Auditory+Midbrain+Implant.">Auditory Cortical Responses to Electrical Stimulation of the Inferior Colliculus: Implications for an Auditory Midbrain Implant.</a> Journal of Neurophysiology. 96, 975-988 (2006).</li><li>Otto, K. J., Rousche, P. J., Kipke, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microstimulation+in+auditory+cortex+provides+a+substrate+for+detailed+behaviors.">Microstimulation in auditory cortex provides a substrate for detailed behaviors.</a> Hearing research. 210, 112-117 (2005).</li><li>Gai, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+Tones+in+Reproducible+Noise+Maskers+by+Rabbits+and+Comparison+to+Detection+by+Humans.">Detection of Tones in Reproducible Noise Maskers by Rabbits and Comparison to Detection by Humans.</a> JARO. 8, 522-538 (2007).</li><li>Miller, C. A., Woodruff, K. E., Pfingst, B. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+responses+from+guinea+pigs+with+cochlear+implants.+I.+Electrophysiological+and+psychophysical+measures.">Functional responses from guinea pigs with cochlear implants. I. Electrophysiological and psychophysical measures.</a> Hearing Research. 92, 85-99 (1995).</li><li>Beitel, R. E., Vollmer, M., Snyder, R. L., Schreiner, C. E., Leake, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+and+neurophysiological+thresholds+for+electrical+cochlear+stimulation+in+the+deaf+cat.">Behavioral and neurophysiological thresholds for electrical cochlear stimulation in the deaf cat.</a> Audiology &#38; Neurotology. 5, 31-38 (2000).</li><li>Beitel, R. E., Snyder, R. L., Schreiner, C. E., Raggio, M. W., Leake, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrical+cochlear+stimulation+in+the+deaf+cat:+comparisons+between+psychophysical+and+central+auditory+neuronal+thresholds.">Electrical cochlear stimulation in the deaf cat: comparisons between psychophysical and central auditory neuronal thresholds.</a> J. Neurophysiol. 83, 2145-2162 (2000).</li><li>Vollmer, M., Beitel, R. E., Snyder, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Auditory+detection+and+discrimination+in+deaf+cats:+Psychophysical+and+neural+thresholds+for+intracochlear+electrical+signals.">Auditory detection and discrimination in deaf cats: Psychophysical and neural thresholds for intracochlear electrical signals.</a> Journal of Neurophysiology. 86, 2330-2343 (2001).</li><li>LeDoux, J. E., Cicchetti, P., Xagoraris, A., Romanski, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+lateral+amygdaloid+nucleus:+sensory+interface+of+the+amygdala+in+fear+conditioning.">The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning.</a> Journal of Neuroscience. 10, 1062-1069 (1990).</li><li>McCreery, D. B., Yuen, T. G., Agnew, W. F., Bullara, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+characterization+of+the+effects+on+neuronal+excitability+due+to+prolonged+microstimulation+with+chronically+implanted+microelectrodes.">A characterization of the effects on neuronal excitability due to prolonged microstimulation with chronically implanted microelectrodes.</a> IEEE Transactions on Biomedical Engineering. 44, 931-939 (1997).</li><li>Liu, X., McPhee, G., Seldon, H. L., Clark, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histological+and+physiological+effects+of+the+central+auditory+prosthesis:+surface+versus+penetrating+electrodes.">Histological and physiological effects of the central auditory prosthesis: surface versus penetrating electrodes.</a> Hearing Research. 114, 264-274 (1997).</li><li>Polikov, V. S., Tresco, P. A., Reichert, W. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Response+of+brain+tissue+to+chronically+implanted+neural+electrodes.">Response of brain tissue to chronically implanted neural electrodes.</a> Journal of Neuroscience Methods. 148, 1-18 (2005).</li></ol>

El doctor Antonio Paolini es un Director de Tecnologías de Bioengenesis Pty Ltd, que son los representantes de Australia para las tecnologías de Tucker Davis y el distribuidor australiano de sondas NeuroNexus.

Las técnicas descritas aquí proporcionan un medio para probar una amplia gama de tareas de discriminación con rapidez, con tiempos cortos de capacitación y permitiendo la automatización importante, minimizando así el tiempo necesario para el investigador de procesamiento de datos. Utilizando los datos obtenidos a partir del ECG implantado, el cálculo de la frecuencia cardíaca (FC) el cambio en los momentos de la presentación del estímulo puede ser automatizado. Errores en el procesamiento del ECG (por ejemplo, falta un solo latido del corazón) pueden ser fácilmente identificados ya que producen cambios en las grandes falsamente aparente de la frecuencia cardíaca durante un período muy breve, y la detección de tales errores fácil reduce al mínimo el requisito de tiempo de uso intensivo de revisión manual de los datos . La técnica descrita para la implantación del dispositivo de telemetría ECG consistentemente produce grabaciones con poca o ninguna interferencia (ver Figuras 1 y 2). Sin embargo, las variaciones relativamente pequeñas en la colocación de la iniciativa en la región del mediastino, puede dar lugar a la interferencia de músculo cercanos y en particular la respiración asociada a ruido. Verificación de la correcta colocación de los cables durante el proceso de implantación, sobre todo después de la sutura lleva en vigor, permite ajustes finos de la colocación del cable para minimizar la interferencia. El proceso de implantación del cerebro en el núcleo coclear es difícil. Mediante el uso de presentaciones en serie de ruido de paso de banda filtrada de varias gamas de frecuencia, en lugar de ruido de banda ancha como se ha utilizado anteriormente 3, las respuestas de las poblaciones de células en los sitios de los electrodos puede ser rápidamente crítica en términos de frecuencia de respuesta más bien que el ruido menos específica respuesta. La capacidad de identificar rápidamente cuando una gama suficiente de las poblaciones de células de frecuencias sintonizadas son accesibles es fundamental en la investigación cuando la discriminación estímulo eléctrico se está probando. Si es insuficiente frecuencia de distribución se obtiene, a continuación, la comparación entre la estimulación de las zonas de frecuencia distintos simplemente no es posible. No obstante, el proceso yade la frecuencia de amplitud en la cartografía respuesta sigue siendo fundamental para ofrecer detalles sobre la amplitud de ajuste de las poblaciones de células y se debe realizar antes de fijar el electrodo en su lugar. En la formación del comportamiento y las pruebas, la inclusión de un no-estímulo (o silencio) período entre los ensayos, previo al inicio del estímulo, permite que la respuesta al inicio del estímulo inicial para ser examinados. Cuando se utiliza la estimulación nerviosa eléctrica, una respuesta al inicio del estímulo proporciona evidencia de la simple detección del estímulo. Así, cuando no hay respuesta inicio del estímulo, pero una respuesta cuando el estímulo alternancia segundo se introduce, se puede deducir que sólo el último estímulo puede ser detectado. Sin inclusión de tal período de silencio, no habría ninguna manera de determinar que el estímulo anterior no fue detectado. Una limitación de esta técnica de las pruebas de comportamiento es que la ausencia de fiebre aftosa, los choques entregado después de la presentación de la neural estimulación puede conducir al desarrollo de la especificidad en el miedo condicionado, de tal manera que el miedo sólo se expresa cuando el estímulo acústico se presenta. Es decir, el animal puede aprender que los efectos particulares sensoriales de estimulación neuronal se asocian con no recibir un choque del pie. En contraste, la entrega de los pies de los choques después de la presentación de la estimulación neuronal podría conducir a un miedo condicionado del estímulo neural en sí, distinta de las propiedades de sonido como el estímulo neural pueda tener. Los resultados obtenidos si se excluye un pie al choque después de la estimulación neuronal ciertamente proveen una evidencia más fuerte para el estímulo neuronal es similar al sonido que los que utilizan un pie al choque después de la estimulación neuronal, como en el primer caso, miedo condicionado se ha generalizado a partir de acústica a la estimulación neuronal. Sin embargo, el riesgo de desarrollar la especificidad de acústica en lugar de la estimulación neuronal está presente. El uso de paso de banda de ruido se filtra como estímulo acústico en lugar de ráfagas de tono puro, el primero de los cualespuede reflejar mejor la experiencia perceptiva de la estimulación neuronal, podría reducir el riesgo de tal especificidad en desarrollo. Sin embargo, tal procedimiento introduce la variable adicional de ancho de banda del filtro, lo que afectará a tareas de discriminación. Una limitación adicional asociado con cualquier implantación crónica neuronal, tal como se requiere para las pruebas de comportamiento, es el cambio en la función del electrodo o el tejido neural asociado con el tiempo. La estimulación del tejido neuronal puede conducir tanto a la supresión temporal de la actividad neuronal y 13 cambios en los tejidos como la pérdida de respuesta de las células del tejido cerebral 14 y directa al electrodo 15. El método descrito para la implantación y las pruebas de comportamiento proporciona un medio para poner a prueba tanto la detección y la discriminación de estímulos acústicos y eléctricos con un breve entrenamiento, y la capacidad para ejercer el control de la frecuencia de ensayo. La técnica de usar el cambio en los recursos humanos como una medicióne de miedo condicionado puede ser aplicable a las pruebas no sólo auditivo, sino más en general para cualquier prueba sensorial en el que los estímulos pueden ser presentados para cualquier período discreto, y en el que la detección de la discriminación sensorial deseada.

<table border="1"><tbody><tr><td> Nombre </td><td> Empresa </td><td> Modelo </td><td> Comentarios </td></tr><tr><td> PowerLab </td><td> ADInstruments </td><td> ML880 </td><td> Registra datos recibidos del transmisor implantado TR40 </td></tr><tr><td> SmartCtrl tarjeta controladora </td><td> Med Asociados </td><td> DIG-716B </td><td> Controla la cámara de pruebas de comportamiento, incluyendo choque del pie </td></tr><tr><td> Cámara modular prueba de comportamiento </td><td> Med Asociados </td><td> ENV-009 </td><td> Prueba de tamaño de la cámara: 30,5 cm x 39,4 cm </td></tr><tr><td> Generador de estímulos aversivos </td><td> Med Asociados </td><td> ENV-410B </td><td> Ofrece aversivo pies de choque para el piso de metal, barras de la jaula a través de una unidad de estado sólido Scrambler </td></tr><tr><td> Atenuador programable </td><td> TDT </td><td> PA5 </td><td> Controla la amplitude de señal entregada acústico para asegurar amplitud estables a través de frecuencias </td></tr><tr><td> El controlador del altavoz electrostático </td><td> TDT </td><td> ED1 </td><td> Unidades de los altavoces electrostáticos (EC1, ES1) </td></tr><tr><td> De campo libre del altavoz electrostático </td><td> TDT </td><td> ES1 </td><td> Los sonidos se presentan con este altavoz en la cámara de prueba de comportamiento </td></tr><tr><td> Junto altavoz electrostático </td><td> TDT </td><td> EC1 </td><td> Los sonidos se presentan con este altavoz durante la cirugía de implante neural </td></tr><tr><td> Estimulador de la estación base </td><td> TDT </td><td> RX7 </td><td> Controles de la entrega de la estimulación nerviosa eléctrica (se utiliza con MS16) </td></tr><tr><td> Microstimulator </td><td> TDT </td><td> MS16 </td><td> Ofrece varios canales de estimulación neuronal eléctrica </td></tr><tr><td> Procesamiento de estación base </td><td> TDT </td><td> RZ2 </td><td> Los registros de actividad neuronal durante la implantación del cerebro (utilizando PZ2 preamplificador) </td></tr><tr><td> Preamplificador </td><td> TDT </td><td> PZ2-256 </td><td> 256-canal preamplificador de alta impedancia </td></tr><tr><td> Receptor del equipo de telemetría </td><td> Telemetría de Investigación </td><td> TR162 </td><td> Recibe la señal digital a partir de TR40, y se convierte en salida amplificada analógica </td></tr><tr><td> ECG implantable dispositivo de telemetría </td><td> Telemetría de Investigación </td><td> TR40 </td><td> El transmisor implantado el dispositivo, el muestreo de 2 kHz </td></tr><tr><td> Multifunción procesador </td><td> Tucker Davis tecnologías (TDT) </td><td> RX6 </td><td> Se utiliza para generar estímulos acústicos </td></tr><tr><td> Vertex Castavaria </td><td> Vertex Dental </td><td></td><td> Acrílico dental utilizado para fijar el electrodo en lugar </td></tr><tr><td> Kwik-Sil adhesiva, de baja viscosidad </td><td> World Precision Instruments </td><td></td><td> Elastómero de silicona se utiliza para recubrir los mangos de los electrodos </td></tr><tr><td> Multicanal electrodo </td><td> NeuroNexus </td><td> a2x16-10mm 100-500-413 </td><td> El 2-vástago de 32 canales de electrodos extracelulares utilizados para la implantación. Los sitios de los electrodos se han activado para producir un recubrimiento de óxido de iridio en preparación para la estimulación. </td></tr></tbody></table>

behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach

Preparaciones agudas de origen animal se han utilizado en la investigación prospectiva, la investigación de los diseños de los electrodos y las técnicas de estimulación para su integración en las prótesis auditivas neuronales, tales como los implantes auditivos de tronco cerebral 1-3 y los implantes auditivos del cerebro medio 4,5. Mientras que los experimentos agudos pueden dar la penetración inicial de la eficacia del implante, para probar los animales crónicamente implantados y despierto proporciona la ventaja de examinar las propiedades psicofísicas de las sensaciones inducida mediante dispositivos implantados 6,7. Varias técnicas como la recompensa basada en el condicionamiento operante 6-8, 9.11 de evitación condicionada, o condicionamiento clásico de miedo 12 se han utilizado para proporcionar una confirmación de la detección del comportamiento de un atributo de estímulo relevante. La selección de una técnica se refiere a aspectos de balance, incluidas la eficiencia del tiempo (a menudo pobres en base recompensa enfoques), la capacidad de probar una pluralidad deestímulo atribuye al mismo tiempo (limitado en evitación condicionada), y la fiabilidad de la medida de estímulos repetidos (una restricción potencial cuando se emplean medidas fisiológicas). Aquí, un método temor condicionamiento conductual clásica se presenta lo que puede ser utilizado para probar simultáneamente tanto la detección de un estímulo, y la discriminación entre dos estímulos. Ritmo cardíaco se utiliza como una medida de la respuesta de miedo, lo que reduce o elimina el requisito de tiempo de codificación de vídeo para el comportamiento de congelación o de otras medidas tales (aunque estas medidas podrían ser incluidos para proporcionar evidencia convergente). Los animales fueron condicionados uso de estas técnicas en tres sesiones de acondicionamiento de 2 horas, cada uno proporcionando 48 ensayos de estímulo. 48-posteriores sesiones de evaluación del ensayo se utilizaron luego para la prueba de detección de cada estímulo en pares presentados, y la discriminación entre los estímulos de prueba miembros de cada par. Este método de comportamiento se presenta enel contexto de su utilización en la investigación auditiva protésica. La implantación de dispositivos de telemetría electrocardiograma se muestra. Tras la implantación de electrodos cerebrales en el núcleo coclear, guiado por el seguimiento de las respuestas neuronales a los estímulos acústicos, y la fijación del electrodo en el lugar para el uso crónico se muestran del mismo modo.

Watch this Scientific Journal Video about Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach at

Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach

La aplicación de un paradigma temor condicionamiento clásico de comportamiento para auditivo protésico investigación en ratas se ha descrito. Este paradigma proporciona un mecanismo para identificar tanto la detección de, y la discriminación entre, acústica diferente y los estímulos eléctricos utilizando la frecuencia cardíaca como medida de resultado.

Determinación del comportamiento de discriminación de estímulos acústicos par de estímulos auditivos y de corriente mediante el condicionamiento clásico y el enfoque del ritmo cardíaco

Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural ...

behavioral-determination-stimulus-pair-discrimination-auditory

Research

Education

JoVE Core

JoVE Journal

Electrical Engineering

Neuroscience

Unit 1

Frequency Response

SCIENTISTS IN ACTION

14.4K vistas.  La Trobe University. La aplicación de un paradigma temor condicionamiento clásico de comportamiento para auditivo protésico investigación en ratas se ha descrito. Este paradigma proporciona un mecanismo para identificar tanto la detección de, y la discriminación entre, acústica diferente y los estímulos eléctricos utilizando la frecuencia cardíaca como medida de resultado.

Video: Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach

Behavioural Pharmacology in Classical Conditioning of the Proboscis Extension Response in Honeybees (Apis mellifera)

Honeybees (Apis mellifera) are well known for their communication and orientation skills and for their impressive learning capability1,2. Because the survival of a honeybee colony depends on the exploitation of food sources, forager bees learn and memorize variable flower sites as well as their profitability. Forager bees can be easily trained in natural settings where they forage at a feeding site and learn the related signals such as odor or color. Appetitive associative learning can also be studied under controlled conditions in the laboratory by conditioning the proboscis extension response (PER) of individually harnessed honeybees3,4. This learning paradigm enables the study of the neuronal and molecular mechanisms that underlie learning and memory formation in a simple and highly reliable way5-12. A behavioral pharmacology approach is used to study molecular mechanisms. Drugs are injected systemically to interfere with the function of specific molecules during or after learning and memory formation13-16.
Here we demonstrate how to train harnessed honeybees in PER conditioning and how to apply drugs systemically by injection into the bee flight muscle.

Behavioural Pharmacology in Classical Conditioning of the Proboscis Extension Response in Honeybees Apis mellifera

We demonstrate how to implement a behavioral pharmacology method in an appetitive olfactory conditioning paradigm in honeybees (Apis mellifera) by systemic application of drugs. This method allows investigation of the mechanisms underlying learning and memory formation in a simple and reliable way.

Farmacología del Comportamiento en el condicionamiento clásico de la respuesta de Extensión probóscide en abejas de la miel ( Apis mellifera)

Honeybees (Apis mellifera) are well known for their communication and orientation skills and for their impressive learning capability1,2. Because the ...

Investigación

Neurociencias

A Lightweight, Headphones-based System for Manipulating Auditory Feedback in Songbirds

Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and sensorimotor plasticity1. Consistent sensory perturbations result in compensatory changes in motor output, reflecting changes in feedforward motor control that reduce the experienced feedback error. By quantifying how different sensory feedback errors affect human behavior, prior studies have explored how visual signals are used to recalibrate arm movements2,3 and auditory feedback is used to modify speech production4-7. The strength of this approach rests on the ability to mimic naturalistic errors in behavior, allowing the experimenter to observe how experienced errors in production are used to recalibrate motor output.
Songbirds provide an excellent animal model for investigating the neural basis of sensorimotor control and plasticity8,9. The songbird brain provides a well-defined circuit in which the areas necessary for song learning are spatially separated from those required for song production, and neural recording and lesion studies have made significant advances in understanding how different brain areas contribute to vocal behavior9-12. However, the lack of a naturalistic error-correction paradigm - in which a known acoustic parameter is perturbed by the experimenter and then corrected by the songbird - has made it difficult to understand the computations underlying vocal learning or how different elements of the neural circuit contribute to the correction of vocal errors13.
The technique described here gives the experimenter precise control over auditory feedback errors in singing birds, allowing the introduction of arbitrary sensory errors that can be used to drive vocal learning. Online sound-processing equipment is used to introduce a known perturbation to the acoustics of song, and a miniaturized headphones apparatus is used to replace a songbird's natural auditory feedback with the perturbed signal in real time. We have used this paradigm to perturb the fundamental frequency (pitch) of auditory feedback in adult songbirds, providing the first demonstration that adult birds maintain vocal performance using error correction14. The present protocol can be used to implement a wide range of sensory feedback perturbations (including but not limited to pitch shifts) to investigate the computational and neurophysiological basis of vocal learning.

We describe the design and assembly of miniaturized headphones suitable for replacing a songbird&#x2019;s natural auditory feedback with a manipulated acoustic signal. Online sound processing hardware is used to manipulate song output, introduce real-time errors in auditory feedback via the headphones, and drive vocal motor learning.

Un peso ligero, Auriculares basada Sistema de Manipulación de retroalimentación auditiva en Songbirds

Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and ...

Functional Imaging of Auditory Cortex in Adult Cats using High-field fMRI

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal models, including monkeys, ferrets, bats, rodents, and cats. In order to draw suitable parallels between human and animal models of auditory function, it is important to establish a bridge between human functional imaging studies and animal electrophysiological studies. Functional magnetic resonance imaging (fMRI) is an established, minimally invasive method of measuring broad patterns of hemodynamic activity across different regions of the cerebral cortex. This technique is widely used to probe sensory function in the human brain, is a useful tool in linking studies of auditory processing in both humans and animals and has been successfully used to investigate auditory function in monkeys and rodents. The following protocol describes an experimental procedure for investigating auditory function in anesthetized adult cats by measuring stimulus-evoked hemodynamic changes in auditory cortex using fMRI. This method facilitates comparison of the hemodynamic responses across different models of auditory function thus leading to a better understanding of species-independent features of the mammalian auditory cortex.

Functional studies of the auditory system in mammals have traditionally been conducted using spatially-focused techniques such as electrophysiological recordings. The following protocol describes a method of visualizing large-scale patterns of evoked hemodynamic activity in the cat auditory cortex using functional magnetic resonance imaging.

Imágenes funcionales de la corteza auditiva en los gatos adultos el uso de alto campo fMRI

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal ...

High Resolution Quantitative Synaptic Proteome Profiling of Mouse Brain Regions After Auditory Discrimination Learning

The molecular synaptic mechanisms underlying auditory learning and memory remain largely unknown. Here, the workflow of a proteomic study on auditory discrimination learning in mice is described. In this learning paradigm, mice are trained in a shuttle box Go/NoGo-task to discriminate between rising and falling frequency-modulated tones in order to avoid a mild electric foot-shock. The protocol involves the enrichment of synaptosomes from four brain areas, namely the auditory cortex, frontal cortex, hippocampus, and striatum, at different stages of training. Synaptic protein expression patterns obtained from trained mice are compared to na&#239;ve controls using a proteomic approach. To achieve sufficient analytical depth, samples are fractionated in three different ways prior to mass spectrometry, namely 1D SDS-PAGE/in-gel digestion, in-solution digestion and phospho-peptide enrichment. 
High-resolution proteomic analysis on a mass spectrometer and label-free quantification are used to examine synaptic protein profiles in phospho-peptide-depleted and phospho-peptide-enriched fractions of synaptosomal protein samples. A commercial software package is utilized to reveal proteins and phospho-peptides with significantly regulated relative synaptic abundance levels (trained/na&#239;ve controls). Common and differential regulation modes for the synaptic proteome in the investigated brain regions of mice after training were observed. Subsequently, meta-analyses utilizing several databases are employed to identify underlying cellular functions and biological pathways.

The identification of molecules and pathways controlling synaptic plasticity and memory is still a major challenge in neuroscience. Here, a workflow is described addressing the relative quantification of synaptic proteins supposedly involved in the molecular reorganization of synapses during learning and memory consolidation in an auditory learning paradigm.

Alta Resolución cuantitativa Synaptic proteoma perfiles de cerebro de ratón Regiones Después de discriminación auditiva de aprendizaje

The molecular synaptic mechanisms underlying auditory learning and memory remain largely unknown. Here, the workflow of a proteomic study on auditory ...

The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain undergoes rapid organizational change and is similar to accelerated brain changes that occur during the third trimester in humans. This model of fetal alcohol spectrum disorders (FASDs) produces severe brain damage, mimicking the amount and pattern of binge-drinking that occurs in some pregnant alcoholic mothers. We describe the use of trace eyeblink classical conditioning (ECC), a higher-order variant of associative learning, to assess long-term hippocampal dysfunction that is typically seen in alcohol-exposed adult offspring. At 90 days of age, rodents were surgically prepared with recording and stimulating electrodes, which measured electromyographic (EMG) blink activity from the left eyelid muscle and delivered mild shock posterior to the left eye, respectively. After a 5 day recovery period, they underwent 6 sessions of trace ECC to determine associative learning differences between alcohol-exposed and control rats. Trace ECC is one of many possible ECC procedures that can be easily modified using the same equipment and software, so that different neural systems can be assessed. ECC procedures in general, can be used as diagnostic tools for detecting neural pathology in different brain systems and different conditions that insult the brain.

Trace eyeblink classical conditioning (ECC) was used to assess hippocampal-dependent associative learning in adult rats that were administered a high concentration (11.9% v/v) of alcohol during early neonatal brain development. In general, ECC procedures are sound diagnostic tools for detecting brain dysfunction across many psychological and biomedical settings.

El uso de condicionamiento de clásico de Eyeblink rastro para evaluar disfunción hipocampal en un modelo de rata de trastornos del espectro alcohólico Fetal

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain ...

Drosophila Courtship Conditioning As a Measure of Learning and Memory

Many insights into the molecular mechanisms underlying learning and memory have been elucidated through the use of simple behavioral assays in model organisms such as the fruit fly, Drosophila melanogaster. Drosophila is useful for understanding the basic neurobiology underlying cognitive deficits resulting from mutations in genes associated with human cognitive disorders, such as intellectual disability (ID) and autism. This work describes a methodology for testing learning and memory using a classic paradigm in Drosophila known as courtship conditioning. Male flies court females using a distinct pattern of easily recognizable behaviors. Premated females are not receptive to mating and will reject the male&#39;s copulation attempts. In response to this rejection, male flies reduce their courtship behavior. This learned reduction in courtship behavior is measured over time, serving as an indicator of learning and memory. The basic numerical output of this assay is the courtship index (CI), which is defined as the percentage of time that a male spends courting during a 10 min interval. The learning index (LI) is the relative reduction of CI in flies that have been exposed to a premated female compared to na&#239;ve flies with no previous social encounters. For the statistical comparison of LIs between genotypes, a randomization test with bootstrapping is used. To illustrate how the assay can be used to address the role of a gene relating to learning and memory, the pan-neuronal knockdown of Dihydroxyacetone phosphate acyltransferase (Dhap-at) was characterized here. The human ortholog of Dhap-at, glyceronephosphate O-acyltransferase (GNPT), is involved in rhizomelic chondrodysplasia punctata type 2, an autosomal-recessive syndrome characterized by severe ID. Using the courtship conditioning assay, it was determined that Dhap-at is required for long-term memory, but not for short-term memory. This result serves as a basis for further investigation of the underlying molecular mechanisms.

Drosophila Courtship Conditioning As a Measure of Learning and Memory

This protocol describes a Drosophila learning and memory assay called courtship conditioning. This classic assay is based on a reduction of male courtship behavior after sexual rejection by a non-receptive premated female. This natural form of behavioral plasticity can be used to test learning, short-term memory, and long-term memory.

Drosophila condicionamiento del corte como una medida de aprendizaje y memoria

Many insights into the molecular mechanisms underlying learning and memory have been elucidated through the use of simple behavioral assays in model ...

Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice

Three vigilance states dominate mammalian life: wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. As more neural correlates of behavior are identified in freely moving animals, this three-fold subdivision becomes too simplistic. During wakefulness, ensembles of global and local cortical activities, together with peripheral parameters such as pupillary diameter and sympathovagal balance, define various degrees of arousal. It remains unclear the extent to which sleep also forms a continuum of brain states-within which the degree of resilience to sensory stimuli and arousability, and perhaps other sleep functions, vary gradually-and how peripheral physiological states co-vary. Research advancing the methods to monitor multiple parameters during sleep, as well as attributing to constellations of these functional attributes, is central to refining our understanding of sleep as a multifunctional process during which many beneficial effects must be executed. Identifying novel parameters characterizing sleep states will open opportunities for novel diagnostic avenues in sleep disorders.
We present a procedure to describe dynamic variations of mouse non-REM sleep states via the combined monitoring and analysis of electroencephalogram (EEG)/electrocorticogram (ECoG), electromyogram (EMG), and electrocardiogram (ECG) signals using standard polysomnographic recording techniques. Using this approach, we found that mouse non-REM sleep is organized into cycles of coordinated neural and cardiac oscillations that generate successive 25-s intervals of high and low fragility to external stimuli. Therefore, central and autonomic nervous systems are coordinated to form behaviorally distinct sleep states during consolidated non-REM sleep. We present surgical manipulations for polysomnographic (i.e., EEG/EMG combined with ECG) monitoring to track these cycles in the freely sleeping mouse, the analysis to quantify their dynamics, and the acoustic stimulation protocols to assess their role in the likelihood of waking up. Our approach has already been extended to human sleep and promises to unravel common organizing principles of non-REM sleep states in mammals.

Here, we present experimental and analytical procedures to describe the temporal dynamics of the neural and cardiac variables of non-REM sleep in mice, which modulate sleep responsiveness to acoustic stimuli.

Cuantificación de la dinámica infrarroja de la potencia espectral y la frecuencia cardíaca en ratones dormidos

Three vigilance states dominate mammalian life: wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. As more neural correlates of behavior ...

Desensitization and Recovery of Crayfish Photoreceptors Upon Delivery of a Light Stimulus

A method to study desensitization and recovery of crayfish photoreceptors is presented. We performed intracellular electrical recordings of photoreceptor cells in isolated eyestalks using the discontinuous single electrode-switched voltage-clamp configuration. First, with a razor blade we made an opening in the dorsal cornea to get access to the retina. Thereafter, we inserted a glass electrode through the opening, and penetrated a cell as reported by the recording of a negative potential. Membrane potential was clamped at the photoreceptor's resting potential and a light-pulse was applied to activate currents. Finally, the two light-flash protocol was employed to measure current desensitization and recovery. The first light-flash triggers, after a lag period, the transduction ionic current, which after reaching a peak amplitude decays towards a desensitized state; the second flash, applied at varying time intervals, assesses the state of the light-activated conductance. To characterize the light-elicited current, three parameters were measured: 1) latency (the time elapsed between light flash delivery and the moment in which current achieves 10% of its maximum value); 2) peak current; and 3) desensitization time constant (exponential time constant of the current decay phase). All parameters are affected by the first pulse.
To quantify recovery from desensitization, the ratio p2/p1 was employed versus time between pulses. p1 is the peak current evoked by the first light-pulse, and p2 is the peak current evoked by the second pulse. These data were fitted to a sum of exponential functions. Finally, these measurements were carried out as function of circadian time.

A protocol for the study of desensitization and sensitivity recovery of crayfish photoreceptors as a function of circadian time is presented.

Desensibilización y recuperación de fotorreceptores de cangrejo de río tras la entrega de un estímulo ligero

A method to study desensitization and recovery of crayfish photoreceptors is presented. We performed intracellular electrical recordings of photoreceptor ...

An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice

Olfaction is the predominant sensory modality in mice and influences many important behaviors, including foraging, predator detection, mating, and parenting. Importantly, mice can be trained to associate novel odors with specific behavioral responses to provide insight into olfactory circuit function. This protocol details the procedure for training mice on a Go/No-Go operant learning task. In this approach, mice are trained on hundreds of automated trials daily for 2&#8211;4 weeks and can then be tested on novel Go/No-Go odor pairs to assess olfactory discrimination, or be used for studies on how odor learning alters the structure or function of the olfactory circuit. Additionally, the mouse olfactory bulb (OB) features ongoing integration of adult-born neurons. Interestingly, olfactory learning increases both the survival and synaptic connections of these adult-born neurons. Therefore, this protocol can be combined with other biochemical, electrophysiological, and imaging techniques to study learning and activity-dependent factors that mediate neuronal survival and plasticity.

Here, we train mice on an associative learning task to test odor discrimination. This protocol also allows for studies on learning-induced structural changes in the brain.

Una prueba objetiva y Reproducible de aprendizaje olfativo y discriminación en ratones

Olfaction is the predominant sensory modality in mice and influences many important behaviors, including foraging, predator detection, mating, and ...

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice

Cochlear implants (CIs) are neuroprosthetic devices that can provide a sense of hearing to deaf people. However, a CI cannot restore all aspects of hearing. Improvement of the implant technology is needed if CI users are to perceive music and perform in more natural environments, such as hearing out a voice with competing talkers, reflections, and other sounds. Such improvement requires experimental animals to better understand the mechanisms of electric stimulation in the cochlea and its responses in the whole auditory system. The mouse is an increasingly attractive model due to the many genetic models available. However, the limited use of this species as a CI model is mainly due to the difficulty of implanting small electrode arrays. More details about the surgical procedure are therefore of great interest to expand the use of mice in CI research.
In this report, we describe in detail the protocol for acute deafening and cochlear implantation of an electrode array in the C57BL/6 mouse strain. We demonstrate the functional efficacy of this procedure with electrically-evoked auditory brainstem response (eABR) and show examples of facial nerve stimulation. Finally, we also discuss the importance of including a deafening procedure when using a normally hearing animal. This mouse model provides a powerful opportunity to study genetic and neurobiological mechanisms that would be of relevance for CI users.

Animal models of cochlear implants can advance knowledge of the technological bases of treating permanent sensorineural hearing loss with electrical stimulation. This study presents a surgical protocol for acute deafening and cochlear implantation of an electrode array in mice as well as the functional assessment with auditory brainstem response.

Cirugía de implante coclear y eléctricamente evocada médula oblonga auditivo respuesta grabaciones en ratones C57BL/6

Cochlear implants (CIs) are neuroprosthetic devices that can provide a sense of hearing to deaf people. However, a CI cannot restore all aspects of ...