Kriss Franklin, Amanda Pollard and Justine Shaffer assisted in animal training and data collection. Sarah Freeman and Alisa Ivanova contributed to data analysis. This study is supported by WVU School of Medicine Start-Up, NIH/NIGMS U54GM104942, and NIH CoBRE P20GM109098.

The following training paradigm employs the analysis of phase adjustments of the average adult Sprague-Dawley rat. Please ensure that the protocol described herein is in accordance with your institutional animal care guidelines. All procedures in this study were performed in accordance with the Institutional Animal Care and Use Committee (IACUC) and Office for Laboratory Animal Welfare (OLAW) at West Virginia University School of Medicine and abides by the National Institutes of Health guidelines for the use of experimen...

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The rationale for this study was to develop a behavioral task that quantitatively assesses the changes in precise control of asymmetric locomotor behaviors. The existence of the spinal CPG has been functionally demonstrated for some time20, but the anatomical and functional characteristics that describe its mechanism as well as its modulatory inputs from descending or sensory feedback pathways have not been characterized until the past decade6,21,22. The current consensus is that the intrinsic spina...

Post-stroke morbidity in the surviving population includes gross motor impairments that pose a challenge for quantitative evaluation in both humans post stroke and animal models of neurologic impairment1. In the clinical setting, these motor impairments are measured using subjective criteria which are more sensitive to severe rather than moderate impairment exhibited by the majority of patients. Similarly, such subjective assessments of post-injury motor behavior in animals are common, e.g., the Basso, Beattie, and Bresnahan (BBB) locomotor scale method2,3. While these subjective evaluation methods are helping translation between gait rehabilitation studies in quadruped animal models and humans, the details of motor deficits associated with activity of separate muscle groups are not assessed. Moreover, the assessment of motor cortical contribution to locomotion, as the putative culprit of motor deficit in cerebrovascular accident, can only be obtained indirectly even using the most novel automated quantitative methods4,5, as they rely on open-field or linear walking tasks. These tasks do not require cortical contribution and can be performed by the neural mechanisms of the spinal cord, i.e., the central pattern generator (CPG) network which is spared in most animal models of neural damage, e.g., spinalized animals6-8. Essential cortical contribution to these spinal mechanisms has been experimentally implicated in tasks that require anticipated postural adjustments9 and reaching10, as well as precise stepping10.
Moreover, most neurological damage is asymmetric; for example, stroke causes hemiparesis, i.e., weakness on one side of the body, which results in an asymmetric gait11-14. The asymmetry of hemiplegic gait is produced by asymmetric spatiotemporal muscle activation most significantly manifested in the shortening of the extensor-associated stance phase and the lengthening of the flexor-associated swing phase of the step cycle on the paretic side15,16. This trend has not yet been explored across a range of locomotor speeds in healthy or paretic animals. In the current study, we employed the analysis of phase duration characteristics17 that describes the relationship between the duration of swing or stance phases as a function of cycle duration in each step. The obtained linear regression model was then further described with an analysis of asymmetry across all limbs.
We report a novel low-cost method for assessing the activity of descending cortical inputs in the motor system of quadruped animals based on a precise stepping locomotor task. This task is designed to challenge the motor cortex by imposing demands on foot placement over a natural range of walking speeds. In addition, foot-placement requirements are manipulated to preferentially challenge the left or right side of the motor system. In a similar locomotor task, Metz &#38; Whishaw (2009) examined the rates of failure, the number of missed steps on irregular rung walkway, in rats. Our method is complimentary to this previous study, and it details the quality of phase control in &#34;successful&#34; steps18.

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asymmetric walkway: a novel behavioral assay for studying asymmetric locomotion

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for quantifying locomotor deficits in rodents is to measure minute disturbances of unconstrained gait overground (e.g., manual BBB score or automated CatWalk). However, cortical inputs are not required for the generation of basic locomotion produced by the spinal central pattern generator (CPG). Thus, unconstrained walking tasks test locomotor deficits due to motor cortical impairment only indirectly. In this study, we propose a novel, precise foot-placement locomotor task that evaluates cortical inputs to the spinal CPG. An instrumented peg-way was used to impose symmetrical and asymmetrical locomotor tasks mimicking lateralized movement deficits. We demonstrate that shifts from equidistant inter-stride lengths of 20% produce changes in the forelimb stance phase characteristics during locomotion with preferred stride length. Furthermore, we propose that the asymmetric walkway allows for measurements of behavioral outcomes produced by cortical control signals. These measures are relevant for the assessment of impairment after cortical damage.

Figure 2 shows the analysis of asymmetry during the locomotor tasks for a single representative subject. The values were calculated for all conditions using Equation 1 and 2 from all subjects individually (Figure 2) and from composite data of 8 female Sprague-Dawley rats (250 - 400 g, Figure 3). Generally, the modulation of the forelimb stance phase was lesser for the side to which the locomotion condition was favored (short ISL), consist...

Watch this Scientific Journal Video about Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion at JoVE.com

Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Here, we present a protocol to quantify precise stepping in rodents. Cortical and the spinal central pattern generator signals are required for precise foot-placement during obstructed locomotion. We report here the novel constrained walking task that directly examines precise stepping behavior.

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for ...

This video reports a novel low-cost method for assessing gait asymmetries in rats, using a precise locomotor limb-positioning task. The phase durations over a range of walking speeds of the quadrupedal gait are used to calculate an index to score the animals'abilities. Our rationale was to develop a behavioral task that quantitatively assesses the changes in precise control for symmetrical locomotor behaviors.This task offers an opportunity to discern the contributions of a descending pathway to the locomotor phase regulation. For example, simultaneous recordings or stimulation in the motor cortex would report as contribution to the modulation of muscle phases in this task. Build the apparatus as an open-topped plastic box with aluminum supports at each corner.Include a frame formed of grooved aluminium railing to provide flexible opportunities for peg placement. The placement of the pegs defines the imposed stride length on the animal. In each of the four corners, put a 20-centimeter square platform.The space between the platforms should accommodate the distance traversed by at least one full step cycle. To create a gait condition, attach aluminum pegs to the rails. These function as footholds for the rat's stride.The pegs should be pre-bent to two point five centimeters from the tip, and should be one centimeter in diameter. Secure the pegs with sliding brackets which can be adjusted with a screwdriver, and, thus, precisely position the footholds. After positioning the footholds, make sure the distances are correct, and that they are on the same horizontal level.Standardize the peg positions for three stepping tasks. First, make a symmetric motor task with 15-centimeter stride lengths by setting the left and right interstride lengths to seven point five centimeters. Second, create a symmetric condition with an interstride challenge by changing those lengths to six centimeters, and, thus, changing the stride to 12 centimeters.Thirdly, create an asymmetric task with a stride length of 15 centimeters. Adjust the position between the pegs to make the interstride length uneven by 20%The task has two configurations with either the left or right interstride being shorter. Thus, each walkway side can represent a separate gait condition.Now, to the side of the apparatus, position an HD camera that can record 60 frames per second. Adjust the field of view to cover about seven steps, and not include the steps closest to the platforms. First, prepare the training environment.Set the interstride lengths to just one centimeter, and place a reward on each platform. Now, let the rat freely explore the new environment for about five minutes. Next, guide the animal across the peg arrangement by presenting it with the reward.When the rat reaches a platform, in addition to the food reward, provide a verbal reward, and pet it on the back. Come right here, right here. You're so close.After five training runs, increase the space between the pegs by one or two centimeters for the next five runs. The goal is to gradually extend the peg distance until the symmetric 15-centimeter stride is accomplished. If the rat is having trouble learning the task, it will be evident from inconsistent stepping with frequent stops and crouching posture.Whenever an increased peg spacing induces anxiety or discomfort, just readjust the pegs to their previous positions and repeat that level of training. It is possible to train and then test the same rat in a single day if the rat is motivated. When the rat has learned the task, its walking will be consistent, without stops or missteps.Its head-bobbing will be minimal, its back will be arched, and its tail will be raised. Rapid stepping with little speed variability, however, is usually a sign that the rat is using a gallop rather than a walk. This behavior should be preventable by training the rat to move at lower speeds.From the camera's view, it is essential that each limb be visible at the onset and offset of the stance phase. When these criteria are all met, testing may commence. For the tests, use the four standardized peg configurations with a randomized session design, including breaks, to avoid adaptation to the task.Details are provided in the text protocol. Save the videos, and use video editing software to cull the walking bouts for analysis. The 60-frame per second rate is essential to the task scoring.For each walking bout, score the onset and offset of the kinematic phases. This can be done in a variety of software by frame-by-frame basis. In this case, custom software written in MATLAB is employed.Stance onset is scored when there is a loss of motion blur. Stance offset is scored when there is first evidence of motion blur. Once the swing phases are all counted, plot them as a function of the corresponding step cycle using a MATLAB script.Data was collected from eight subjects and analyzed as described. Seen here is the asymmetry analysis for one subject. The combined analysis of the eight subjects shows that, generally, the modulation of the forelimb stance phase was lessened for the side to which the locomotion condition was favored, and vice-versa.ANOVA with a conservative Bonferroni correction showed a significant difference between the two asymmetric conditions in the asymmetry indices, including the anterior horizontal symmetry index. The right vertical asymmetry showed a trend towards difference between the two conditions. Similarly, a significant difference was found in the diagonality index between two asymmetric conditions.No differences were found in this index between other tasks, based on ANOVA with a post hoc t test, and no alpha correction. Animal models of focal stroke and spinal cord amolesion cause movement deficits akin to those observed clinically, and lesioning of the cortical spinal track in this way impedes this precise stepping behavior. This may result in a delay in the onset of consecutive locomotor phases, which is consistent with an asymmetry in both the step-length ratio and the single limb support time observed in post-stroke patients.The animals which acquired the task are now prime for locomotor assessment in models of cortical injuries such as middle cerebral artery occlusion and traumatic brain injury.

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8.7K vistas.  West Virginia University School of Medicine. This video reports a novel low-cost method for assessing gait asymmetries in rats, using a precise locomotor limb-positioning task. The phase durations over a range of walking speeds of the quadrupedal gait are used to calculate an index to score the animals'abilities. Our rationale was to develop a behavioral task that quantitatively assesses the changes in precise control for symmetrical locomotor behaviors.This task offers an opportunity to discern the contributions of a descending ...

Video: Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Here, we present a protocol to quantify precise stepping in rodents. Cortical and the spinal central pattern generator signals are required for precise foot-placement during obstructed locomotion. We report here the novel constrained walking task that directly examines precise stepping...

spinal cord lateral hemisection and asymmetric behavioral assessments in adult rats

Spinal Cord Lateral Hemisection and Asymmetric Behavioral Assessments in Adult Rats

Here we describe surgical procedures to produce a reliable spinal cord lateral hemisection (HX) at the 9th thoracic level in adult rats and neurobehavioral assessments designed for detecting asymmetric deficits after such a unilateral...

studying cell rolling trajectories on asymmetric receptor patterns

Studying Cell Rolling Trajectories on Asymmetric Receptor Patterns

We describe a protocol to observe and analyze cell rolling trajectories on asymmetric receptor-patterned substrates. The resulting data are useful for engineering of receptor-patterned substrates for label-free cell separation and...

antibody uptake assay for tracking notch/delta endocytosis during the asymmetric division of zebrafish radial glia progenitors

Antibody Uptake Assay for Tracking Notch/Delta Endocytosis During the Asymmetric Division of Zebrafish Radial Glia Progenitors

This work develops an antibody uptake assay for imaging intra-lineage Notch/DeltaD signaling in dividing radial glia progenitors of the embryonic zebrafish...

behavioral assessments of spontaneous locomotion in a murine mptp-induced parkinson's disease model

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson&#039;s Disease Model

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

asymmetric thermoelectrochemical cell for harvesting low-grade heat under isothermal operation

Asymmetric Thermoelectrochemical Cell for Harvesting Low-grade Heat under Isothermal Operation

Low-grade heat is abundant, but its efficient recovery is still a great challenge. We report an asymmetric thermoelectrochemical cell using graphene oxide as a cathode and polyaniline as an anode with KCl as the electrolyte. This cell works under isothermal heating, exhibiting a high heat-to-electricity conversion efficiency in low-temperature...

optimized negative staining: a high-throughput protocol for examining small and asymmetric protein structure by electron microscopy

Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy

More than half of proteins are small proteins (molecular mass &#60;200 kDa) that are challenging for both electron microscope imaging and three-dimensional reconstructions. Optimized negative staining is a robust and high-throughput protocol to obtain high contrast and relatively high resolution (~1 nm) images of small asymmetric proteins or complexes under different physiological...

phase behavior of charged vesicles under symmetric and asymmetric solution conditions monitored with fluorescence microscopy

Phase Behavior of Charged Vesicles Under Symmetric and Asymmetric Solution Conditions Monitored with Fluorescence Microscopy

Experiments on phase separated giant unilamellar vesicles (GUVs) frequently neglect physiological solution conditions. This work presents approaches to study the effect of high-salinity buffer on liquid-liquid phase separation in charged multicomponent GUVs as a function of trans-membrane solution asymmetry and...

a mouse model for vascular cognitive impairment and dementia based on needle-guided asymmetric bilateral common carotid artery stenosis

Author Spotlight: Advancing Vascular Cognitive Impairment and Dementia Studies with a Reliable Mouse Model

The needle method of asymmetric bilateral common carotid artery stenosis is proposed to create a mouse model for vascular cognitive impairment and dementia. It results in longer-term outcomes compared to previously established models and is compatible with live MRI. Visual representation demonstrating the procedure provides guidance for mastering the...

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis

in situ transmission electron microscopy with biasing and fabrication of asymmetric crossbars based on mixed-phased a-vox

In Situ Transmission Electron Microscopy with Biasing and Fabrication of Asymmetric Crossbars Based on Mixed-Phased a-VOx

Presented here is a protocol for analyzing nanostructural changes during in&#160;situ biasing with transmission electron microscopy (TEM) for a stacked metal-insulator-metal structure. It has significant applications in resistive switching crossbars for the next generation of programmable logic circuits and neuromimicking hardware, to reveal their underlying operation mechanisms and practical...

In Situ Transmission Electron Microscopy with Biasing and Fabrication of Asymmetric Crossbars Based on Mixed-Phased a-VOx

behavioral approaches to studying innate stress in zebrafish

Behavioral Approaches to Studying Innate Stress in Zebrafish

This manuscript describes a simple method to measure stress behaviorally in adult zebrafish. The approach takes advantage of the innate tendency that zebrafish prefer the bottom half of a tank when in a stressful state. We also describe methods for coupling the assay with...

electrotaxis assay: a method to observe locomotion in c. elegans

Researchers can trigger on-demand movement in C. elegans by applying an electric field that worms sense and respond to.&#160; This video introduces electrotactic behavior and shows a sample protocol that is done in a microfluidic...

Electrotaxis Assay: A Method to Observe Locomotion in C. elegans

synthetic methodology for asymmetric ferrocene derived bio-conjugate systems via solid phase resin-based methodology

Synthetic Methodology for Asymmetric Ferrocene Derived Bio-conjugate Systems via Solid Phase Resin-based Methodology

The synthesis of asymmetric species of ferrocene is challenging using solution techniques.  This report focuses on the methods carried out to produce a ferrocene-biotin bioconjugate using facile and clean reactions accomplished via solid-phase synthesis.  Incorporation of a thiolate moiety is shown to impart the ability for immobilization on gold...

microfluidic imaging flow cytometry by asymmetric-detection time-stretch optical microscopy (atom)

Microfluidic Imaging Flow Cytometry by Asymmetric-detection Time-stretch Optical Microscopy ATOM

This protocol describes the implementation of an asymmetric-detection time-stretch optical microscopy system for single-cell imaging in ultrafast microfluidic flow and its applications in imaging flow cytometry.

Microfluidic Imaging Flow Cytometry by Asymmetric-detection Time-stretch Optical Microscopy (ATOM)

single step isolation of extracellular vesicles from large-volume samples with a bifurcated a4f microfluidic device

Author Spotlight: Asymmetric Field Flow Fractionation for Bioreactor Integration

Extracellular vesicles hold immense promise for biomedical applications, but current isolation methods are time-consuming and impractical for clinical use. In this study, we present a microfluidic device that enables the direct isolation of extracellular vesicles from large volumes of biofluids in a continuous manner with minimal steps.

Microfluidic Device for Continuous Extracellular Vesicle Isolation from Human Urine

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fly climbing assay: a method to test general locomotion in drosophila melanogaster

This video describes a simple method to quantify fly locomotion and shows the climbing assay performed.&#160; The fly climbing assay is a general test of motor function which relies on a negative geotaxis...

Fly Climbing Assay: A Method to Test General Locomotion in Drosophila melanogaster

a novel behavioral assay to investigate gustatory responses of individual, freely-moving bumble bees (bombus terrestris)

A Novel Behavioral Assay to Investigate Gustatory Responses of Individual, Freely-moving Bumble Bees Bombus terrestris

A novel behavioral assay is described for investigating the short term gustatory responses of the mouthparts of freely-moving bumble bees (Bombus terrestris) toward nutrients and toxins in solution.

A Novel Behavioral Assay to Investigate Gustatory Responses of Individual, Freely-moving Bumble Bees (Bombus terrestris)

A Needle Model for Vascular Cognitive Impairment Studies in Mice

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an assay for measuring the effects of ethanol on the locomotion speed of caenorhabditis elegans

An Assay for Measuring the Effects of Ethanol on the Locomotion Speed of Caenorhabditis elegans

C. elegans is a useful model for studying the effects of ethanol on behavior. We present a behavioral assay that quantifies the effects of ethanol on the locomotion speed of crawling worms; both initial sensitivity and the development of acute functional tolerance to ethanol can be measured with this assay.

An Assay for Measuring the Effects of Ethanol on the Locomotion Speed of Caenorhabditis elegans

battery of behavioral tests assessing general locomotion, muscular strength, and coordination in mice

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

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

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

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

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

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

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

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

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

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal&#39;s wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2&#39; x 2&#39; box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the ...

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

A Behavioral Assay for Investigating the Role of Spatial Memory During Instinctive Defense in Mice

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often stereotyped actions elicited in response to innately aversive sensory stimuli, but their success requires enough flexibility for adapting to different spatial environments, which can change rapidly. Here, we describe a behavioral assay to evaluate the influence of learned spatial knowledge on defensive behaviors in mice. We have adapted the widely used Barnes maze spatial memory assay to investigate how mice navigate to a shelter during escape responses to innately aversive sensory stimuli in a novel environment, and how they adapt to acute changes in the environment. This new assay is an ethological paradigm that does not require training and exploits the natural exploration patterns and navigation strategies in mice. We propose that the set of protocols described here are a powerful means of studying goal-directed behaviors and stimulus-triggered navigation, which should be of interest to both the fields of instinctive behaviors and spatial memory.

This protocol describes a behavioral assay, based on the Barnes maze test, to study how instinctive defensive actions are modified by the knowledge of spatial environment.

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often ...

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive decline, such as Alzheimer&#39;s disease (AD), have become a promising tool to elucidate the underlying mechanisms and promote the therapeutic advances. An important step is the validation and characterization of expected behavioral abnormality in the models, in the case of AD, cognitive decline. The long-term behavioral investigations of laboratory animals to study the effect of aging demand substantial efforts from researchers. The IntelliCage system is a high-throughput and cost-effective test battery for mice that eliminates the need for daily human handling. Here, we describe how the system is utilized in the long-term phenotyping of a genetic Alzheimer&#39;s disease model, specifically focusing on the cognitive functions. The experiment employs repeated battery of tests that assess spatial learning and executive functions. This cost-effective age-dependent phenotyping allows us to identify the transient and/or permanent effects of genes on various cognitive aspects.

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer&#039;s Disease, Using IntelliCage

This paper describes a protocol for cognitive assessments for genetic models of the Alzheimer&#39;s disease using the IntelliCage system, which is a high throughput automated behavioral monitoring system with operant conditioning.

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive ...