Ces travaux sont appuyés par une subvention découverte accordée à BDC par le Conseil de recherches en sciences naturelles et en génie du Canada (CSERN; RGPIN 311680) et une subvention de fonctionnement à BDC des Instituts de recherche en santé du Canada (IRSC; MOP-93796). RAK a reçu l’appui d’une bourse d’études supérieures de l’Ontario, et l’ALC a reçu l’appui d’une subvention CREATE du CSERN. L’appareil expérimental décrit dans ce manuscrit a été appuyé par la Fondation canadienne pour l’innovation. Le Fonds d’excellence en recherche Canada First (BrainsCAN) a également soutenu ce fonds.

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N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Voluntary+modification+of+automatic+arm+movements+evoked+by+motion+of+a+visual+target.">Voluntary modification of automatic arm movements evoked by motion of a visual target.</a> Experimental Brain Research. 130 (2), 159-168 (2000).</li><li>Gaveau, V., 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=Automatic+online+control+of+motor+adjustments+in+reaching+and+grasping.">Automatic online control of motor adjustments in reaching and grasping.</a> Neuropsychologia. 55 (1), 25-40 (2014).</li><li>Day, B. L., Brown, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+for+subcortical+involvement+in+the+visual+control+of+human+reaching.">Evidence for subcortical involvement in the visual control of human reaching.</a> Brain A Journal of Neurology. 124, 1832-1840 (2001).</li><li>Pruszynski, A. J., 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=Stimulus-locked+responses+on+human+arm+muscles+reveal+a+rapid+neural+pathway+linking+visual+input+to+arm+motor+output.">Stimulus-locked responses on human arm muscles reveal a rapid neural pathway linking visual input to arm motor output.</a> European Journal of Neuroscience. 32 (6), 1049-1057 (2010).</li><li>Corneil, B. D., Olivier, E., Munoz, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual+responses+on+neck+muscles+reveal+selective+gating+that+prevents+express+saccades.">Visual responses on neck muscles reveal selective gating that prevents express saccades.</a> Neuron. 42 (5), 831-841 (2004).</li><li>Wood, D. K., Gu, C., Corneil, B. D., Gribble, P. L., Goodale, 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=Transient+visual+responses+reset+the+phase+of+low-frequency+oscillations+in+the+skeletomotor+periphery.">Transient visual responses reset the phase of low-frequency oscillations in the skeletomotor periphery.</a> European Journal of Neuroscience. 42 (3), 1919-1932 (2015).</li><li>Gu, C., Wood, D. K., Gribble, P. L., Corneil, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Trial-by-Trial+Window+into+Sensorimotor+Transformations+in+the+Human+Motor+Periphery.">A Trial-by-Trial Window into Sensorimotor Transformations in the Human Motor Periphery.</a> Journal of Neuroscience. 36 (31), 8273-8282 (2016).</li><li>Kozak, R. A., Kreyenmeier, P., Gu, C., Johnston, K., Corneil, B. 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C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cross-species+comparison+of+anticipatory+and+stimulus-driven+neck+muscle+activity+well+before+saccadic+gaze+shifts+in+humans+and+nonhuman+primates.">Cross-species comparison of anticipatory and stimulus-driven neck muscle activity well before saccadic gaze shifts in humans and nonhuman primates.</a> Journal of Neurophysiology. 114 (2), 902-913 (2015).</li><li>Franklin, D. W., Reichenbach, A., Franklin, S., Diedrichsen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporal+evolution+of+spatial+computations+for+visuomotor+control.">Temporal evolution of spatial computations for visuomotor control.</a> Journal of Neuroscience. 36 (8), 2329-2341 (2016).</li><li>Krekelberg, B., Vatakis, A., Kourtzi, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Implied+motion+from+form+in+the+human+visual+cortex.">Implied motion from form in the human visual cortex.</a> Journal of Neurophysiology. 94 (6), 4373-4386 (2005).</li><li>Gribble, P. 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Les humains ont une capacité remarquable, en cas de besoin, de générer des actions rapides et visuellement guidées à des latences qui approchent des retards de conduction minimaux et éfferents. Nous avons précédemment décrit les réponses verrouillées par stimulus (REFLEX) sur le membre supérieur comme une nouvelle mesure pour les réponses visuomotricesrapides 6,9,10. Bien qu’ils aient été bénéfiques pour fourn...

Lorsque nous remarquons un message sur notre téléphone cellulaire, nous sommes invités à effectuer une portée visuellement guidée pour prendre notre téléphone et lire le message. Les caractéristiques visuelles telles que la forme et la taille du téléphone sont transformées en commandes motrices nous permettant d’atteindre l’objectif avec succès. De telles transformations visuomotrices peuvent être étudiées dans des conditions de laboratoire, ce qui permet un degré élevé de contrôle. Toutefois, il existe des scénarios où le temps de réponse est important, par exemple, attraper le téléphone s’il devait tomber. Les études en laboratoire sur les comportements visuomotrices rapides reposent souvent sur des paradigmes cibles déplacés où les mouvements en cours sont modifiés en plein vol à la suite d’un certain changement de position cible (p. ex., voir réf.1,2). Bien que de telles corrections en ligne puissent se produire en <150 ms3, il est difficile de déterminer le moment exact de la sortie visuomotrice rapide en utilisant la cinématique seule en raison des caractéristiques de filtrage à faible passage du bras, et parce que la sortie visuomotrice rapide remplace un mouvement déjà en plein vol. De telles complications entraînent une incertitude quant aux substrats sous-jacents aux réponses visuomotrices rapides (voir l’réf.4 pour examen). Quelques études suggèrent que les structures subcortical telles que le colliculus supérieur, plutôt que les secteurs corticals fronto-pariétals, puissent initier des corrections enligne 5.
Cette incertitude concernant les substrats neuronaux sous-jacents peut être due, au moins en partie, à l’absence d’un biomarqueur fiable pour la production du système visuomotor rapide. Récemment, nous avons décrit une mesure des réponses visuomotrices rapides qui peuvent être générées à partir de postures statiques et enregistrées par électromyographie (EMG). Les réponses verrouillées par stimulus (REFLEX) sont des rafales verrouillées dans le temps de l’activité d’EMG qui précèdent le mouvement volontaire6,7,évoluant uniformément ~100 ms après le début de stimulus. Comme son nom l’indique, les reflex sont évoqués par le début du stimulus, persistant même si un mouvement éventuel estretenu 8 ou se déplace dans la direction opposée9. En outre, les reflex évoqués par le déplacement cible dans un paradigme dynamique sont associés à des corrections en ligne de latence pluscourtes 10. Ainsi, les reflex fournissent une mesure objective pour étudier systématiquement la production d’un système visuomotor rapide impliqué dans les TT à latence courte, car ils peuvent être générés à partir d’une posture statique et analyse à partir d’autres signaux EMG sans rapport avec la phase initiale de la réponse visuomotrice rapide.
L’objectif de l’étude actuelle est de présenter un paradigme d’atteinte visuellement guidé qui suscite solidement les reflex. Des études antérieures portant sur le SLR ont signalé des taux de détection inférieurs à 100 % chez les participants, même lorsqu’ils utilisent des enregistrements intramusculairesplus invasifs 6,8,9. Les faibles taux de détection et la dépendance à l’égard des enregistrements invasifs limitent l’utilité des mesures slr dans les études futures sur le système visuomotrice rapide dans la maladie ou tout au long de la durée de vie. Bien que certains sujets peuvent tout simplement ne pas exprimer reflex, les stimuli et les paradigmes comportementaux utilisés précédemment peuvent ne pas avoir été idéal pour évoquer le Reflex. Les rapports précédents des reflex ont généralement utilisé des paradigmes dans lequel les participants génèrent des portées visuellement guidées vers statique, apparaissant soudainement cibles6,9. Cependant, un système visuomotor rapide est le plus probablement nécessaire dans les scénarios où l’on doit interagir rapidement avec un objet qui tombe ou vole, ce qui conduit à se demander si le déplacement plutôt que des stimuli statiques peut mieux évoquer reflex. Par conséquent, nous avons adapté un paradigme cible mobile utilisé pour étudier les mouvementsoculaires 11, et l’avons combiné avec une tâche pro / anti visuellement guidée atteignant utilisé pour examiner le REFLEX9. Par rapport aux résultats des paradigmes utilisésprécédemment 6,8,9, il a été constaté que les reflex dans le paradigme cible émergent évolué plus tôt, atteint des magnitudes plus élevées, et étaient plus répandues dans notre échantillon participant. Dans l’ensemble, le paradigme cible émergent favorise l’expression de réponses visuomotrices rapides à un point tel que des mesures objectives de l’EMG peuvent être prises de manière fiable avec des enregistrements de surface, potentialisation des études au sein des populations cliniques et tout au long de la durée de vie. En outre, le paradigme cible émergent peut être modifié de nombreuses façons différentes, favorisant des investigations plus approfondies sur les facteurs sensoriels, cognitifs et moteurs qui favorisent ou modifient les réponses visuomotrices rapides.

<table>
	<tbody>
		<tr>
			<td>Bagnoli-8 Desktop Surface EMG System</td>
			<td>Delsys Inc.</td>
			<td></td>
			<td>Another reaching apparatus may be used</td>
		</tr>
		<tr>
			<td>Kinarm End-Point Robot</td>
			<td>Kinarm, Kingston, Ontario, Canada</td>
			<td></td>
			<td>Another reaching apparatus may be used</td>
		</tr>
		<tr>
			<td>MATLAB (version R2016a) Stateflow and Simulink applications</td>
			<td>The MathWorks, Inc., Natick, Massachusetts, United States</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PROPixx projector</td>
			<td>VPIXX Saint-Bruno, QC, Canada</td>
			<td></td>
			<td>This is a custom built addon for the Kinarm. Other displays may be used.</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td>Resolution: 1920 x 1080. Standard viewing monitors may also be used.</td>
		</tr>
	</tbody>
</table>

an emerging target paradigm to evoke fast visuomotor responses on human upper limb muscles

Pour atteindre un objet vu, l’information visuelle doit être transformée en commandes motrices. Les informations visuelles telles que la couleur, la forme et la taille de l’objet sont traitées et intégrées dans de nombreuses zones du cerveau, puis finalement relayées à la périphérie motrice. Dans certains cas, une réaction est nécessaire aussi vite que possible. Ces transformations visuomotrices rapides, et leurs substrats neurologiques sous-jacents, sont mal comprises chez l’homme car elles n’ont pas de biomarqueur fiable. Les réponses verrouillées par stimulus (REFLEX) sont de courtes latences (<100 ms) des éclats d’activité électromyographique (EMG) représentant la première vague de recrutement musculaire influencée par la présentation visuelle de stimulus. Les reflex fournissent une production quantifiable de transformations visuomotrices rapides, mais les reflex n’ont pas été observés de façon constante chez tous les sujets dans des études antérieures. Nous décrivons ici un nouveau paradigme comportemental mettant en vedette l’émergence soudaine d’une cible en mouvement sous un obstacle qui évoque constamment des reflex robustes. Les participants humains ont généré des portées visuellement guidées vers ou loin de la cible émergente à l’aide d’un manipulandum robotique tandis que les électrodes de surface enregistrait l’activité EMG du muscle majeur pectoralis. Par rapport aux études précédentes qui ont étudié les reflex à l’aide de stimuli statiques, les reflex évoqués avec ce paradigme cible émergent étaient plus grands, ont évolué plus tôt et étaient présents chez tous les participants. Les temps de réaction de portée (TR) ont également été accélérés dans le paradigme cible émergent. Ce paradigme offre de nombreuses possibilités de modification qui pourraient permettre une étude systématique de l’impact de diverses manipulations sensorielles, cognitives et motrices sur les réponses visuomotrices rapides. Dans l’ensemble, nos résultats démontrent qu’un paradigme cible émergent est capable d’évoquer constamment et vigoureusement l’activité au sein d’un système visuomotor rapide.

Stimulus réponses verrouillées (Reflex) sont de brèves rafales de temps d’activité musculaire verrouillé au début de stimulus qui évoluent bien avant la plus grande volée de recrutement musculaire associée à l’apparition du mouvement. La nature verrouillée du Reflex a produit un « baguage » de l’activité musculaire visible à ~ 100 ms lors de la visualisation de tous les essais triés pour le temps de réaction (RT) (Figure 1a, mis en évidence par des boîtes grises). ...

Watch this Scientific Journal Video about An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles at JoVE.com

An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles

Présenté ici est un paradigme comportemental qui suscite des réponses visuomotrices rapides robustes sur les muscles des membres supérieurs humains au cours des portées visuellement guidées.

Un paradigme cible émergent pour évoquer des réponses visuomotrices rapides sur les muscles des membres supérieurs humains

To reach towards a seen object, visual information has to be transformed into motor commands. Visual information such as the object&#8217;s color, shape, ...

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4.2K vues.  Western University. Présenté ici est un paradigme comportemental qui suscite des réponses visuomotrices rapides robustes sur les muscles des membres supérieurs humains au cours des portées visuellement guidées.

Vidéo: An Emerging Target Paradigm to Evoke Fast Visuomotor Responses on Human Upper Limb Muscles

Recording Behavioral Responses to Reflection in Crayfish

Social behavior depends on sensory input from the visual, mechanical and olfactory systems. One important issue concerns the relative roles of each sensory modality in guiding behavior. The role of visual inputs has been examined by isolating visual stimuli from mechanical and chemosensory stimuli. In some studies (Bruski &amp; Dunham, 1987: Delgado-Morales et al., 2004) visual inputs have been removed with blindfolds or low light intensity, and effects of remaining sensory modalities have been elucidated. An alternative approach is to study the effects of visual inputs in the absence of any appropriate mechanical and chemosensory cues. This approach aims to identify the exclusive role of visual inputs. 
We have used two methods to provide visual stimuli to crayfish without providing chemical and mechanical cues. In one method, crayfish are videotaped in an aquarium where half of the walls are covered in mirrors to provide a reflective environment, and the other half are covered in a non-reflective (matte finish) plastic. This gives the crayfish a choice between reflective and non-reflective environments. The reflective environment provides visual cues in the form of reflected images of the crayfish as it moves throughout half of the tank; these visual cues are missing from the non-reflective half of the tank. An alternative method is to videotape the behavior of crayfish in an aquarium separated by a smaller chamber at each end, with a crayfish in one small chamber providing visual cues and an inert object in the opposite small chamber providing visual input from a non-moving, non-crayfish source. 
Our published results indicate that responses of crayfish to the reflective environment depend on socialization and dominance rank. Socialized crayfish spent more time in the reflective environment and exhibited certain behaviors more frequently there than in the non-reflective environment; isolated crayfish showed no such differences. Crayfish that were housed in same-sex pairs developed a social rank of either dominant or subordinate. Responses to reflection differed between dominant and subordinate crayfish (May &amp; Mercier, 2006; May &amp; Mercier, 2007). Dominant crayfish spent more time on the reflective side, entered reflective corners more frequently and spent more time in reflective corners compared to the non-reflective side. Subordinate crayfish walked in reverse more often on the reflective side than on the non-reflective side. Preliminary data suggest similar effects from visual cues provided by a crayfish in a small adjoining chamber (May et al., 2008).

We have developed two methods for studying effects of visual cues on behavior in the absence of tactile and chemical cues. One method involves videotaping responses of crayfish to reflective walls in an aquarium; the other examines effects of visual inputs provided by a live crayfish behind a transparent partition.

Enregistrement des réponses comportementales à la réflexion chez les écrevisses

Social behavior depends on sensory input from the visual, mechanical and olfactory systems.  One important issue concerns the relative roles of each ...

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Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals

Mechanical dissociation of neurons from the central nervous system has the advantage that presynaptic boutons remain attached to the isolated neuron of interest. This allows for examination of synaptic transmission under conditions where the extracellular and postsynaptic intracellular environments can be well controlled. A vibration-based technique without the use of proteases, known as vibrodissociation, is the most popular technique for mechanical isolation. A micropipette, with the tip fire-polished to the shape of a small ball, is placed into a brain slice made from a P1-P21 rodent. The micropipette is vibrated parallel to the slice surface and lowered through the slice thickness resulting in the liberation of isolated neurons. The isolated neurons are ready for study within a few minutes of vibrodissociation. This technique has advantages over the use of primary neuronal cultures, brain slices and enzymatically isolated neurons including: rapid production of viable, relatively mature neurons suitable for electrophysiological and imaging studies; superior control of the extracellular environment free from the influence of neighboring cells; suitability for well-controlled pharmacological experiments using rapid drug application and total cell superfusion; and improved space-clamp in whole-cell recordings relative to neurons in slice or cell culture preparations. This preparation can be used to examine synaptic physiology, pharmacology, modulation and plasticity. Real-time imaging of both pre- and postsynaptic elements in the living cells and boutons is also possible using vibrodissociated neurons. Characterization of the molecular constituents of pre- and postsynaptic elements can also be achieved with immunological and imaging-based approaches.

This report demonstrates a technique for mechanical isolation of individual viable neurons retaining attached presynaptic boutons. Vibrodissociated neurons have the advantages of rapid production, excellent pharmacological control and improved space-clamp without influence from neighboring cells. This method can be used for imaging of synaptic elements and patch-clamp recording.

Vibrodissociation des neurones à partir de tranches de cerveau de rongeurs pour étudier la transmission synaptique et de l&#39;image terminaisons présynaptiques

Mechanical dissociation of neurons from the central nervous system has the advantage that presynaptic boutons remain attached to the isolated neuron of ...

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar tasks. Participants' behavior during task performance in an fMRI scanner can then be correlated to the brain activity using the blood-oxygen-level-dependent signal. We measure behavior to be able to sort correct trials, where the subject performed the task correctly and then be able to examine the brain signals related to correct performance. Conversely, if subjects do not perform the task correctly, and these trials are included in the same analysis with the correct trials we would introduce trials that were not only for correct performance. Thus, in many cases these errors can be used themselves to then correlate brain activity to them. We describe two complementary tasks that are used in our lab to examine the brain during suppression of an automatic responses: the stroop1 and anti-saccade tasks. The emotional stroop paradigm instructs participants to either report the superimposed emotional 'word' across the affective faces or the facial 'expressions' of the face stimuli1,2. When the word and the facial expression refer to different emotions, a conflict between what must be said and what is automatically read occurs. The participant has to resolve the conflict between two simultaneously competing processes of word reading and facial expression. Our urge to read out a word leads to strong 'stimulus-response (SR)' associations; hence inhibiting these strong SR's is difficult and participants are prone to making errors. Overcoming this conflict and directing attention away from the face or the word requires the subject to inhibit bottom up processes which typically directs attention to the more salient stimulus. Similarly, in the anti-saccade task3,4,5,6, where an instruction cue is used to direct only attention to a peripheral stimulus location but then the eye movement is made to the mirror opposite position. Yet again we measure behavior by recording the eye movements of participants which allows for the sorting of the behavioral responses into correct and error trials7 which then can be correlated to brain activity. Neuroimaging now allows researchers to measure different behaviors of correct and error trials that are indicative of different cognitive processes and pinpoint the different neural networks involved.

The goal of our research is to correlate behavior to brain activity. Accurate behavioral measures and imaging techniques allow us to elucidate brain-behavior relationships.

Corrélation entre réponses comportementales aux signaux IRMf de cortex préfrontal humain: l&#39;examen des processus cognitifs en utilisant l&#39;analyse des tâches

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar ...

An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila

An experimental method has been developed to investigate the cellular responses to central nervous system (CNS) injury using the fruit-fly Drosophila. Understanding repair and regeneration in animals is a key question in biology. The damaged human CNS does not regenerate, and understanding how to promote the regeneration is one of main goals of medical neuroscience. The powerful genetic toolkit of Drosophila can be used to tackle the problem of CNS regeneration.
A lesion to the CNS ventral nerve cord (VNC, equivalent to the vertebrate spinal cord) is applied manually with a tungsten needle. The VNC can subsequently be filmed in time-lapse using laser scanning confocal microscopy for up to 24 hr to follow the development of the lesion over time. Alternatively, it can be cultured, then fixed and stained using immunofluorescence to visualize neuron and glial cells with confocal microscopy. Using appropriate markers, changes in cell morphology and cell state as a result of injury can be visualized. With ImageJ and purposely developed plug-ins, quantitative and statistical analyses can be carried out to measure changes in wound size over time and the effects of injury in cell proliferation and cell death. These methods allow the analysis of large sample sizes. They can be combined with the powerful genetics of Drosophila to investigate the molecular mechanisms underlying CNS regeneration and repair.

An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila

An injury paradigm using the Drosophila larval ventral nerve cord to investigate central nervous system regeneration and repair is described. Stabbing followed by laser scanning confocal microscopy in time-lapse and fixed specimens, combined with quantitative analysis with purposefully developed software and genetics, are used to investigate the molecular mechanisms of CNS regeneration and repair.

Un paradigme d&#39;enquêter sur les blessures du système nerveux central de réparation de<em&gt; Drosophila</em

An experimental method has been developed to investigate the cellular responses to central nervous system (CNS) injury using the fruit-fly Drosophila. ...

Electrophysiological Method for Recording Intracellular Voltage Responses of Drosophila Photoreceptors and Interneurons to Light Stimuli In Vivo

Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method described here enables the investigator to measure long-lasting (from minutes to hours) high-quality intracellular responses from single Drosophila R1-R6 photoreceptors and Large Monopolar Cells (LMCs) to light stimuli. Because the recording system has low noise, it can be used to study variability among individual cells in the fly eye, and how their outputs reflect the physical properties of the visual environment. We outline all key steps in performing this technique. The basic steps in constructing an appropriate electrophysiology set-up for recording, such as design and selection of the experimental equipment are described. We also explain how to prepare for recording by making appropriate (sharp) recording and (blunt) reference electrodes. Details are given on how to fix an intact fly in a bespoke fly-holder, prepare a small window in its eye and insert a recording electrode through this hole with minimal damage. We explain how to localize the center of a cell's receptive field, dark- or light-adapt the studied cell, and to record its voltage responses to dynamic light stimuli. Finally, we describe the criteria for stable normal recordings, show characteristic high-quality voltage responses of individual cells to different light stimuli, and briefly define how to quantify their signaling performance. Many aspects of the method are technically challenging and require practice and patience to master. But once learned and optimized for the investigator's experimental objectives, it grants outstanding in vivo neurophysiological data.

Electrophysiological Method for Recording Intracellular Voltage Responses of Drosophila Photoreceptors and Interneurons to Light Stimuli In Vivo

Sharp microelectrodes enable accurate electrophysiological characterization of photoreceptor and visual interneuron output in living Drosophila. Here we show how to use this method to record high-quality voltage responses of individual cells to controlled light stimulation. This method is ideal for studying neural information processing in insect compound eyes.

Méthode électrophysiologique de réponses d&#39;enregistrement intracellulaire tension de<em&gt; Drosophila</em&gt; Photorécepteurs et Interneurones à Light Stimuli<em&gt; In Vivo</em

Voltage responses of insect photoreceptors and visual interneurons can be accurately recorded with conventional sharp microelectrodes. The method ...

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development

Investigating potential pharmacodynamic effects in an early phase of central nervous system (CNS) drug research can provide valuable information for further development of new compounds. A computerized and thoroughly validated battery of neuropsychological and neurophysiological tests has been shown to be sensitive to detect drug-induced effects of multiple new and existing compounds. The test battery covers the main CNS domains, which have been shown to respond to drug effects and can be repeatedly administered following drug administration to characterize the concentration-effect profile of a drug.
The standard tests in the battery are saccadic eye movement, smooth pursuit eye movement, the Bowdle visual analog scale (VAS), the Bond and Lader VAS, body sway, adaptive tracking, visual verbal learning, and quantitative electroencephalography (qEEG). However, the test battery is adaptive in nature, meaning that it can be composed and adjusted with tests fit to investigate specific drug classes, or even specific receptors.
Showing effects of new cholinergic drugs designed to have a pro-cognitive outcome has been difficult. The pharmacological challenge model is a tool for early proof-of-pharmacology. Here, a marketed drug is used to induce temporary and reversible disease-like symptoms in healthy subjects, via a pharmacological mechanism related to the disease that is targeted as indication for the new compound. The test battery was implemented to investigate the potential of the nicotinic receptor antagonist mecamylamine to be used as a challenge model for cholinergic dysfunction, as seen in neurodegenerative disorders.
A worsening of scores in a dose dependent manner on the visual verbal learning test (VVLT; a test for learning and memory abilities) and the adaptive tracking test (a measure of visuomotor control and arousal), in particular, showed that the test battery is sensitive to showing acute pharmacodynamic effect after administration of anti-cholinergic drugs.

A validated computerized battery of neuropsychological and neurophysiological tests is used to study pharmacodynamic effects on the central nervous system of newly developed drugs in early phase development. To demonstrate the test battery, the acute effects of mecamylamine and the reversal of these effects by two agonist drugs are described.

Une batterie de tests informatisés pour étudier les effets pharmacodynamiques sur le système nerveux Central des drogues cholinergiques dans la Phase précoce Drug Development

Investigating potential pharmacodynamic effects in an early phase of central nervous system (CNS) drug research can provide valuable information for ...

An In Ovo Model for Testing Insulin-mimetic Compounds

Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and &#946;-cell failure. Various strategies, including the injection of insulin or the usage of insulin-sensitizing drugs, were pursued to treat T2DM or at least reduce the symptoms. In addition, the application of herbal compounds has attracted increasing attention. Thus, it is necessary to find efficient test systems to identify and characterize insulin-mimetic compounds. Here we developed a modified chick embryo model, which enables testing of synthetic compounds and herbal extracts with insulin-mimetic properties. Using a fluorescence microscopy-based primary screen, which quantifies the translocation of Glucose transporter 4 (Glut4) to the plasma membrane, we were able to identify compounds, mainly herbal extracts, which lead to an increase of intracellular glucose concentrations in adipocytes. However, the efficacy of these substances requires further verification in a living organism. Thus, we used an in-ovo approach to identify their blood glucose-reducing properties. The approval by an ethics committee is not needed since the use of chicken embryos during the first two-thirds of embryonic development is not considered an animal experiment. Here, the application of this model is described in detail.

An In Ovo Model for Testing Insulin-mimetic Compounds

In this study, we describe an in-ovo system as a promising tool to test insulin-mimetic compounds in a living organism. The main advantages include adequate throughput rates and acceptable costs, which enable the identification of phytochemicals with insulin-mimetic properties.

Un modèle In Ovo pour tester les composés insulino-mimétiques

Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and ...

FM Dye Cycling at the Synapse: Comparing High Potassium Depolarization, Electrical and Channelrhodopsin Stimulation

FM dyes are used to study the synaptic vesicle (SV) cycle. These amphipathic probes have a hydrophilic head and hydrophobic tail, making them water-soluble with the ability to reversibly enter and exit membrane lipid bilayers. These styryl dyes are relatively non-fluorescent in aqueous medium, but insertion into the outer leaflet of the plasma membrane causes a &#62;40X increase in fluorescence. In neuronal synapses, FM dyes are internalized during SV endocytosis, trafficked both within and between SV pools, and released with SV exocytosis, providing a powerful tool to visualize presynaptic stages of neurotransmission. A primary genetic model of glutamatergic synapse development and function is the Drosophila neuromuscular junction (NMJ), where FM dye imaging has been used extensively to quantify SV dynamics in a wide range of mutant conditions. The NMJ synaptic terminal is easily accessible, with a beautiful array of large synaptic boutons ideal for imaging applications. Here, we compare and contrast the three ways to stimulate the Drosophila NMJ to drive activity-dependent FM1-43 dye uptake/release: 1) bath application of high [K+] to depolarize neuromuscular tissues, 2) suction electrode motor nerve stimulation to depolarize the presynaptic nerve terminal, and 3) targeted transgenic expression of channelrhodopsin variants for light-stimulated, spatial control of depolarization. Each of these methods has benefits and disadvantages for the study of genetic mutation effects on the SV cycle at the Drosophila NMJ. We will discuss these advantages and disadvantages to assist the selection of the stimulation approach, together with the methodologies specific to each strategy. In addition to fluorescent imaging, FM dyes can be photoconverted to electron-dense signals visualized using transmission electron microscopy (TEM) to study SV cycle mechanisms at an ultrastructural level. We provide the comparisons of confocal and electron microscopy imaging from the different methods of Drosophila NMJ stimulation, to help guide the selection of future experimental paradigms.

Synaptic vesicle (SV) cycling is the core mechanism of intercellular communication at neuronal synapses. FM dye uptake and release are the primary means of quantitatively assaying SV endo- and exocytosis. Here, we compare all the stimulation methods to drive FM1-43 cycling at the Drosophila neuromuscular junction (NMJ) model synapse.

FM colorant cyclisme au niveau de la Synapse : en comparant la dépolarisation élevés de Potassium, électrique et Stimulation de la Channelrhodopsin

FM dyes are used to study the synaptic vesicle (SV) cycle. These amphipathic probes have a hydrophilic head and hydrophobic tail, making them ...

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

L’utilisation combinée de Transcranial Direct Current Stimulation et thérapie robotique pour le membre supérieur

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles&#8212;e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill&#8212;and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway&#39;s excitability. First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value.
To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex&#8212;the electrically-elicited analog of the spinal stretch reflex&#8212;in the soleus muscle. Down-conditioning this pathway&#39;s excitability can improve walking in people with spastic gait due to incomplete spinal cord injury. The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to transcranial magnetic stimulation; how it can address various clinical problems; and how it can support research studies of sensorimotor function in health and disease.

The Evoked Potential Operant Conditioning System EPOCS: A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders

The Evoked Potential Operant Conditioning System aids scientific investigation of sensorimotor function and can administer targeted neurobehavioral training that can impact sensorimotor rehabilitation in neuromuscular disorders. This article describes its capabilities and illustrates its application in modifying a simple spinal reflex to achieve lasting improvement in motor function.

L’Evoked Potential Operant Conditioning System (EPOCS) : un outil de recherche et une thérapie émergente pour les maladies neuromusculaires chroniques

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle ...