The auto-training device was constructed by Jason Dunthorn, Uri Tasch, and Dan Tasch at Step Analysis, LLC, with design input support and instructions provided by Robert Hubbard, Richard O&#39;Brien, and Steven Zeiler.
Teresa Duarte of the Champalimaud Centre for the Unknown provided valuable insight and ideas about describing and categorizing mouse reaching actions.

All methods described here have been approved by the ACUC (Animal Care and Use Committee) of the Johns Hopkins University.
1. Preparing mouse cages for use
<ol>
	<li>Create a slotted opening with dimensions of 0.8 cm width and 7 cm height from the base at the front end of each cage, as illustrated in Figure 1. This slot serves as the opening through which the animal will reach. 
	NOTE: The auto-trainer was designed for the use with the standard mouse cage dimensions (as shown in Figure 1) supplied by most animal research supply vendors. Further, the auto-trainer will easily support other cage-types.</li>
	<li>Inside each individual cage, add a platform adjacent to the slot to allow the mice to stand and reach the presented pellets. Ensure that the platform is located above the cage litter floor, approximately 3 cm in height. Use Petri dishes affixed with superglue and capped by a metal sheet approximately 10 cm x 15 cm, however, any flat surface large enough for a mouse to stand on to reach from will suffice.</li>
	<li>Create a vertical notch through the middle of the front of the cage measuring 0.8 cm across and 7 cm high that will allow a mouse to reach his paw out of the cage.</li>
	<li>From a thin sheet of metal, (approximately 2 mm thick) cut a cage gate into rectangles measuring 5 cm x 10 cm to serve as a uniform opening through which the animal is to reach. 
	NOTE: Mice may chew on plastic cages which would change the size of the opening. The mouse will reach through this 0.8 cm slot when the metallic cage gate is placed over the cage&#39;s slotted opening during testing using tape, maintaining the effective width of the slot between cages.</li>
	<li>Cover each cage&#39;s slot with tape when its mouse is not being tested to prevent litter from being expelled from the cage.</li>
</ol>
2. Introducing mice to the reaching motion
<ol>
	<li>Record each mouse&#39;s starting weight and calculate 85% of that value to find their goal weight, rounding up to 20 g if the result is less. Give them a feeding regime to bring them to and then maintain this goal weight.
	<ol>
		<li>Give each mouse 2.5 g of pellets the first day and note any change in their weight 24 h later. 
		NOTE: Weigh the mice once per day and expect a weight drop of 0.25-1 g per day.</li>
		<li>Change each mouse&#39;s daily feed as required, based on this initial change and ongoing changes in each mouse&#39;s weight, in order to induce gradual weight loss (less than 0.8 g lost per day) and then maintain the resulting goal weight. Vary between three to six 500 mg pellets (1.5 to 3.0 g) per day to be effective. 
		NOTE: Mice remain on this diet to maintain their goal weight throughout the protocol.</li>
	</ol>
	</li>
	<li>When a mouse has reached its goal weight, introduce each mouse to the concept of coming up to the gated slot for a supplementary food pellet. Start a training session by placing a 45 mg pellet on the pellet surface, directly in front of the slot, and allow each mouse to retrieve it. Most mice will take to this feeding arrangement within 1-2 days.</li>
	<li>Once the mouse associates an open slot with being fed, encourage them to reach with a paw, rather than the mouth. 
	NOTE: This is the most complex step, taking 1-2 days, and instilling counterproductive behavior in mice by mistake is very easy; please refer to the discussion section for further information and advice.
	<ol>
		<li>Using a pair of tweezers, hold a pellet in the same position the mouse has retrieved pellets previously. As the mouse begins to bite for the pellet, pull it away approximately half a centimeter such that the pellet is out of reach of its mouth. 
		NOTE: A mouse at its goal weight will attempt to retrieve the out-of-reach pellet. Whenever the mouse extends a paw through the slot, reinforce that behavior by allowing it to eat the pellet. Some mice may exhibit a preference for one paw over the other when extending for food.</li>
		<li>While not instrumental to experimentation, record whether the left or right paw is preferred. This may potentially allow for higher overall success rates in the behavioral assay; alternatively, eliminate a variable by forcing each mouse to reach with the same paw. 
		NOTE: Better results are obtained if mice use their preferred paw.</li>
		<li>As each mouse associates extending a paw with eating a pellet, further reinforce that behavior by withholding the pellet in response to attempts to retrieve the pellet with the mouth and tongue. Mice will start to comply with this arrangement over 2 to 3 days.</li>
		<li>Finalize the introduction of the desired paw reaching behavior by placing the 45 mg pellet just under 1 cm from the outer edge of the cage gate, such that the leftmost or rightmost point of the pellet (whether it is to the right or left of the cage slot from the investigator&#39;s perspective, respectively) is tangent to a line extending straight out from the edge of the cage gate&#39;s slot. Allow the mouse to attempt to retrieve the pellet, being vigilant to remove the pellet and prevent its consumption if the mouse should attempt by some other method than paw extension. 
		NOTE: When a mouse consistently extends a paw to grab at and is able to touch the provided pellet, it is ready for testing using the auto-trainer described below and associated behavioral assay. The time from na&#239;ve introductions to being prepared will vary between mice; if there are stragglers that take more than two weeks to understand, they should be excluded from the data set.</li>
	</ol>
	</li>
</ol>
3. Using the auto-trainer
NOTE: Please see Figure 1-3 and the discussion section for a full description of the hardware, software, and the physical actions of the auto-trainer.
<ol>
	<li>Prepare for the training session.
	<ol>
		<li>Calibrate the bait pellet sensor. Click the Run arrow in the LabVIEW interface and note the bait pellet sensor reading both with and without a pellet in place. Click the Stop button to stop this test run and change the bait pellet sensor target to a value between those two readings (Figure 3 and Table 2). Most lighting conditions provide a reading between 1 and 4.</li>
		<li>Place the modified mouse cage on the auto-trainer (Figure 2). Affix the cage gate ( Figure 1) and align the pellet to the edge of the slot as in the manual procedure.</li>
	</ol>
	</li>
	<li>Run the mouse&#39;s training session using the LabVIEW interface.
	<ol>
		<li>Input information as required to record data about the training session (Figure 3 and Table 2).
		<ol>
			<li>Click the Mouse ID field and type the filename of each training session using the computer&#39;s keyboard.</li>
			<li>Click the Total Pellets to Dispense During Routine field to control how many pellets are dispensed for a single experiment (usually 20 - 30). To do so, click the up and down arrows or input the number using the computer&#39;s keyboard.</li>
			<li>Click the Pause After Pellet Number field to set a 5 s pause after the indicated pellet is removed from the diving board. To do so, click the up and down arrows or input the number using the computer&#39;s keyboard.</li>
			<li>Click the Pause Length field to set a pause in between the time a pellet is removed from the diving board and the time a new pellet is dispensed. To do so, click the up and down arrows or input the number using the computer&#39;s keyboard 
			NOTE: Usually 1 s is an appropriate pause time. If the mice are anxious after each pellet is dispensed, it is advisable to increase the pause length using the Pause Length field to 5 s.</li>
			<li>Manually record the distance at which the pellet is placed in the Reach Distance field. To do so, click the up and down arrows or input the number using the computer&#39;s keyboard 
			NOTE: The Size of the Acceleration and Time Arrays is exposed for debugging purposes and may be ignored.</li>
			<li>Click the Folder to Contain Logs field to select the file location to save the collected data.</li>
			<li>Once the information fields have been filled out, click the Run button to begin the training session. The auto-trainer will dispense individual pellets and track whether they fall through the funnel until the total number of pellets has been dispensed, and the last pellet has either been retrieved or dropped by the mouse. The program will stop automatically at this point. If necessary, it can also be stopped prematurely by clicking on the Stop button.</li>
		</ol>
		</li>
		<li>Once the software is set up, place the home-cage of the mouse to be tested on the pedestal and observe the mouse so that you might gauge whether the mouse has indeed learned to attempt the required novel reaching behavior. After clicking the Run button, allow the mouse to investigate the slot and its new, unfamiliar surroundings. 
		NOTE: Similar to when introducing mice to the concept of reaching, expect some mice to be more compliant than others. Mice that have grasped the concept should try to reach within 5-10 min and will associate the movement of the auto-trainer with the presented pellet, as when they associate an uncovered slot with food in the initial stages of this protocol.</li>
	</ol>
	</li>
</ol>

<ol>
	<li>Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+endpoint,+descriptive,+and+kinematic+comparison+of+skilled+reaching+in+mice+(mus+musculus)+with+rats+(rattus+norvegicus).">An endpoint, descriptive, and kinematic comparison of skilled reaching in mice (mus musculus) with rats (rattus norvegicus).</a> Behavior Brain Research. 78, 101-111 (1996).</li><li>Farr, T. D., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+and+qualitative+impairments+in+skilled+reaching+in+the+mouse+(mus+musculus)+after+a+focal+motor+cortex+stroke.">Quantitative and qualitative impairments in skilled reaching in the mouse (mus musculus) after a focal motor cortex stroke.</a> Stroke. 33, 1869-1875 (2002).</li><li>Zeiler, S. R., Krakauer, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+interaction+between+training+and+plasticity+in+the+poststroke+brain.">The interaction between training and plasticity in the poststroke brain.</a> Current Opinion in Neurology. 26, 609-616 (2013).</li><li>Klein, A., Sacrey, L. A., Whishaw, I. Q., Dunnett, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+rodent+skilled+reaching+as+a+translational+model+for+investigating+brain+damage+and+disease.">The use of rodent skilled reaching as a translational model for investigating brain damage and disease.</a> Neuroscience and Biobehavioral Reviews. 36, 1030-1042 (2012).</li><li>Zeiler, S. R., 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=Medial+premotor+cortex+shows+a+reduction+in+inhibitory+markers+and+mediates+recovery+in+a+mouse+model+of+focal+stroke.">Medial premotor cortex shows a reduction in inhibitory markers and mediates recovery in a mouse model of focal stroke.</a> Stroke. 44, 483-489 (2013).</li><li>Becker, A. M., Meyers, E., Sloan, A., Rennaker, R., Kilgard, M., Goldberg, M. 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K., 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=Improved+single+pellet+grasping+using+automated+ad+libitum+full-time+training+robot.">Improved single pellet grasping using automated ad libitum full-time training robot.</a> Behavior Brain Research. 281, 137-148 (2015).</li><li>Ng, K. L., 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=Fluoxetine+maintains+a+state+of+heightened+responsiveness+to+motor+training+early+after+stroke+in+a+mouse+model.">Fluoxetine maintains a state of heightened responsiveness to motor training early after stroke in a mouse model.</a> Stroke. 46 (10), 2951-2960 (2015).</li><li>Whishaw, I. Q., Suchowersky, O., Davis, L., Sarna, J., Metz, G. A., Pellis, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impairment+of+pronation,+supination,+and+body+co-ordination+in+reach-to-grasp+tasks+in+human+parkinson's+disease+(pd)+reveals+homology+to+deficits+in+animal+models.">Impairment of pronation, supination, and body co-ordination in reach-to-grasp tasks in human parkinson's disease (pd) reveals homology to deficits in animal models.</a> Behavior Brain Research. 133, 165-176 (2002).</li><li>Dobrossy, M. D., Dunnett, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+influence+of+environment+and+experience+on+neural+grafts.">The influence of environment and experience on neural grafts.</a> Nature Review Neuroscience. 2, 871-879 (2001).</li><li>Alaverdashvili, M., Foroud, A., Lim, D. H., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&amp;#34;Learned+baduse&amp;#34;+limits+recovery+of+skilled+reaching+for+food+after+forelimb+motor+cortex+stroke+in+rats:+A+new+analysis+of+the+effect+of+gestures+on+success.">&amp;#34;Learned baduse&amp;#34; limits recovery of skilled reaching for food after forelimb motor cortex stroke in rats: A new analysis of the effect of gestures on success.</a> Behavior Brain Research. 188, 281-290 (2008).</li></ol>

Dan Tasch and Uri Tasch of Step Analysis, LLC have manufactured auto-trainer device with payment from Richard J. O'Brien and Steven R. Zeiler.

Our auto-trainer evaluates forelimb reach-to-grasp (prehension) in an automated manner. To achieve this endpoint, many of the parameters designed for the mouse prehension task, including pellet placement, pellet size, and training criteria, have been iterated over several years and adapted from prior protocols2,5,6. The advancement here is the automation of the task using a robot that allows home-cage housing. Home-cage housing ...

Methods to experimentally test a motor skill pre- and post- neurological injury as well as modulate the timing, amount, and type of motor training are important to translational research. Over the last decade, mice, because of the attendant ease of genetic manipulation, have become a popular model system in which to elucidate the mechanisms of motor learning pre- and post- injury. However, behavioral assays in mice have not been optimized in the same way that such assays have been for other mammals (especially rats). Further, there are important differences between the behavior of a mouse and a rat that strongly suggest training the two species in different manners1,2.
Skilled prehensile movements use a hand/paw to place food in the mouth, to manipulate an object, or to use a tool. Indeed, reaching to grasp various objects in daily life is a fundamental function of upper limbs and the reach-to-eat act is a form of prehension that many mammals use. Many of the genetic, physiological, and anatomic changes underpinning prehensile skill acquisition have been well defined in the field3. In translating preclinical findings to clinical outcomes, one needs a relevant test that is efficient and reproducible. Studies of rodent and human reaching demonstrate that prehension behavior is similar in humans and in animals4. Accordingly, these similarities suggest that prehension testing can serve as a translational model for investigating motor learning as well as impairments and treatments of human disease. Therefore, evaluating prehension in mice can offer a powerful tool in translational research studying both health and disease states4.
Unfortunately, the prehension task in mice, even for a small-scale laboratory setting, can be laborious and time consuming. To alleviate this problem, we describe here an automated version of the prehension task. The described task requires mice to extend a single paw through the mouse's home cage frontal slot, pronate the extended paw, grasp the food pellet reward, and pull the pellet back to the cage interior for consumption. The resulting data is presented as either a prehension success or failure. This automation successfully records the data and reduces the burden and time with which researchers must engage the task.

<table><tbody><tr><td>ABS Filament</td><td>Custom 3D Printed</td><td>N/A</td><td>utilized for pellet holder, frame, arm and funnel</td></tr><tr><td>ABS Sheet</td><td>McMaster-Carr</td><td>8586K581</td><td>3/8&quot; thickness; used for platform compononents, positioning stand guides and base</td></tr><tr><td>Adruino Mini</td><td>Adruino</td><td>A000087</td><td>nano version also compatiable as well as other similar microcontrollers</td></tr><tr><td>Bench-Top Adjustable-Height Positioning Stand</td><td>McMaster-Carr</td><td>9967T43</td><td>35 lbs. load capacity</td></tr><tr><td>Clear Acrylic Round Tube</td><td>McMaster-Carr</td><td>8532K14</td><td>ID 3/8&quot;</td></tr><tr><td>Low-Carbon&amp;nbsp;Steel Wire</td><td>McMaster-Carr</td><td>8855K14</td><td>0.148&quot;&amp;nbsp;diameter</td></tr><tr><td>Pellet Dispenser</td><td>Lafayette Instrument: Neuroscience</td><td>80209-45</td><td>with 45 mg interchangeable pellet size wheel and optional stand</td></tr><tr><td>Photointerrupter Breakout Board&amp;nbsp;</td><td>SparkFun</td><td>BOB-09322 ROHS</td><td>designed for Sharp GP1A57HRJ00F</td></tr><tr><td>Reflective Object Sensor</td><td>Fairchild Semiconductor</td><td>QRD1113</td><td>phototransistor output</td></tr><tr><td>Servo Motor</td><td>SparkFun</td><td>S8213</td><td>generic metal gear (micro size)</td></tr><tr><td>Transmissive Photointerrupter</td><td>Sharp</td><td>GP1A57HRJ00F</td><td>gap: 10 mm, slit: 1.8 mm</td></tr></tbody></table>

evaluating skilled prehension in mice using an auto-trainer

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that permits the mouse to reach out of its cage and retrieve food pellets. Minimal food restriction is employed to encourage the mice to perform the food retrieval from the slot. As the mice begin to associate coming to the slot for food, the pellets are manually pulled away to stimulate extension and pronation of their paw to grasp and retrieve the pellet through the frontal slot. When the mice begin to reach for the pellets as they arrive at the slot, the behavioral assay can be performed by measuring the rate at which they successfully grasp and retrieve the desired pellet. They are then introduced to an auto-trainer that automates both the process of providing food pellets for the mouse to grasp, and the recording of successful and failed reaching and grasping attempts. This allows for the collection of reaching data for multiple mice with minimal effort, to be used in experimental analysis as appropriate.

In general, it is recommended that each training session consist of about 20-30 trials, which may be set by the user, run automatically by the auto-trainer and saved into a single log file per session and mouse. Each trial can be run consecutively, right after the other, with 2-5 s of pause. Mice trained on the auto-trainer exhibit an increase in skill over 10 training sessions.
To compare the utility of the auto-trainer to manu...

Watch this Scientific Journal Video about Evaluating Skilled Prehension in Mice Using an Auto-Trainer at JoVE.com

Evaluating Skilled Prehension in Mice Using an Auto-Trainer

Method to assess the impact of training on motor skills is a useful tool. Unfortunately, most behavioral assessments can be labor intensive and/or expensive.We describe here a robotic method of assessing prehension (reach-to-grasp) skill in mice.

We describe a method to introduce na&#239;ve mice to a novel prehension (reach-to-grasp) task. Mice are housed singly in cages with a frontal slot that ...

evaluating-skilled-prehension-in-mice-using-an-auto-trainer

Research

JoVE Journal

Behavior

5.6K Views.  Johns Hopkins University. Method to assess the impact of training on motor skills is a useful tool. Unfortunately, most behavioral assessments can be labor intensive and/or expensive.We describe here a robotic method of assessing prehension (reach-to-grasp) skill in mice. 

Video: Evaluating Skilled Prehension in Mice Using an Auto-Trainer

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

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and retrieve food rewards positioned at a specific location, their motor performance (defined as accuracy and speed) improves progressively over time, and plateaus after persistent training. Once such reaching skill is mastered, its further maintenance does not require constant practice. Here we introduce a single-pellet reaching task to study the acquisition and maintenance of skilled forelimb movements in mice. In this video, we first describe the behaviors of mice that are commonly encountered in this learning and memory paradigm, and then discuss how to categorize these behaviors and quantify the observed results. Combined with mouse genetics, this paradigm can be utilized as a behavioral platform to explore the anatomical underpinnings, physiological properties, and molecular mechanisms of learning and memory.

Persistent practice improves the precision of coordinated movements.&#160;Here we introduce a single-pellet reaching task, which is designed to assess the learning and memory of forelimb skill in mice.&#160;

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

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models.

Mouse models have become increasingly popular in studies of behavioral neuroscience. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. This protocol describes the Pasta Matrix Reaching Task, which is a skilled motor task for use in mouse models of stroke.

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models ...

Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor learning and execution is of critical importance in order to understand the principles and processes that underlie motor function. Here we present a paradigm to study movement acquisition within a daily session of training (within-session) representing the fast learning component and primary acquisition as well as skilled motor learning over several training sessions (between-session) representing the slow learning component and consolidation of the learned task. This behavioral paradigm increases the degree of difficulty and complexity of the motor skill task due to two features: First, the animal realigns its body prior to each pellet retrieval forcing renewed orientation and preventing movement execution from the same angle. Second, pellets are grasped from a vertical post that matches the diameter of the pellet and is placed in front of the cage. This requires a precise grasp for successful pellet retrieval and thus prevents simple pulling of the pellet towards the animal. In combination with novel genetics, imaging and electrophysiological technologies, this behavioral method will aid to understand the morphological, anatomical and molecular underpinnings of motor learning and memory.

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

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

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

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

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

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

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous research determined a profound impact of gentle handling protocols on the well-being of laboratory mice. By introducing clicker training to the keeping of mice, not only do we promote the amicable treatment of mice, but we also enable them to experience cognitive enrichment. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcer, the "click" sound of a clicker, which serves as a time bridge between the strengthened behavior and an upcoming reward. The effective implementation of the clicker training protocol with a cohort of 12 BALB/c inbred mice of each sex proved to be uncomplicated. The mice learned rather quickly when challenged with tasks of the clicker training protocol, and almost all trained mice overcame the challenges they were given (100% of female mice and 83% of male mice). This study has identified that clicker training for mice strongly correlates with reduced fear in the mice during human-mice interactions, as shown by reduced anxiety-related behaviors (e.g., defecation, vocalization, and urination) and fewer depression-like behaviors (e.g., floating). By developing a reliable protocol that can be easily integrated into the daily routine of the keeping of laboratory mice, the lifetime experience of welfare in the mice can be improved substantially.

The development of new refinement strategies for laboratory mice is a challenging task that contributes towards fulfilling the 3R principle. This protocol introduces clicker training as a cognitive enrichment program for laboratory mice.

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous ...

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

Automated Rat Single-Pellet Reaching with 3-Dimensional Reconstruction of Paw and Digit Trajectories

Rodent skilled reaching is commonly used to study dexterous skills, but requires significant time and effort to implement the task and analyze the behavior. Several automated versions of skilled reaching have been developed recently. Here, we describe a version that automatically presents pellets to rats while recording high-definition video from multiple angles at high frame rates (300 fps). The paw and individual digits are tracked with DeepLabCut, a machine learning algorithm for markerless pose estimation. This system can also be synchronized with physiological recordings, or be used to trigger physiologic interventions (e.g., electrical or optical stimulation).

Rodent skilled reaching is commonly used to study dexterous skills, but requires significant time and effort to implement the task and analyze the behavior. We describe an automated version of skilled reaching with motion tracking and three-dimensional reconstruction of reach trajectories.

Rodent skilled reaching is commonly used to study dexterous skills, but requires significant time and effort to implement the task and analyze the ...

Behavioral Training Procedures for Head-fixed Virtual Reality in Mice

Virtual reality (VR) combined with head-fixation is increasingly being utilized in behavioral neuroscience studies as it allows complex behavioral assays to be performed in head-fixed mice. This enables precise behavioral recordings while incorporating various neurophysiological techniques that require head-fixation to minimize movement-related signal noise during neural recordings. However, despite the growing use of VR, there is little published data on the detailed methodology of how to implement it. In this study, a training protocol is developed whereby male and female C57B16/J mice are trained to run down a virtual linear corridor, the length of which is increased from 1-3 m over multiple training sessions. Building upon this foundation, this study investigated the feasibility of mice performing complex behaviors within VR using a Y-maze paradigm. The task required navigating to the arm with black walls from the choice point in the Y-maze. After reaching a criterion of two consecutive days equal to or greater than 70% correct, the mice progressed to increasingly difficult sensory discrimination. The findings provide important details on the methodologies useful for the successful training of mice in VR and demonstrate that mice exhibit learning capabilities in navigating the Y-maze. The methodology presented not only offers insights into training duration in VR-based assays but also underscores the potential for probing intricate behaviors in mice, opening avenues for more comprehensive neuroscience investigations.

The article describes the experimental procedures for the commonly used linear track virtual reality (VR) paradigm in mice as well as determining the feasibility of running complex VR tasks by testing a Y-shaped signal discrimination task.

Virtual reality (VR) combined with head-fixation is increasingly being utilized in behavioral neuroscience studies as it allows complex behavioral assays ...

In Vivo Wireless Optogenetic Control of Skilled Motor Behavior

Fine motor skills are essential in everyday life and can be compromised in several nervous system disorders. The acquisition and performance of these tasks require sensory-motor integration and involve precise control of bilateral brain circuits. Implementing unimanual behavioral paradigms in animal models will improve the understanding of the contribution of brain structures, like the striatum, to complex motor behavior as it allows manipulation and recording of neural activity of specific nuclei in control conditions and disease during the performance of the task. 
Since its creation, optogenetics has been a dominant tool for interrogating the brain by enabling selective and targeted activation or inhibition of neuronal populations. The combination of optogenetics with behavioral assays sheds light on the underlying mechanisms of specific brain functions. Wireless head-mounted systems with miniaturized light-emitting diodes (LEDs) allow remote optogenetic control in an entirely free-moving animal. This avoids the limitations of a wired system being less restrictive for animals' behavior without compromising light emission efficiency. The current protocol combines a wireless optogenetics approach with high-speed videography in a unimanual dexterity task to dissect the contribution of specific neuronal populations to fine motor behavior.

In Vivo Wireless Optogenetic Control of Skilled Motor Behavior

The present protocol describes how to use wireless optogenetics combined with high-speed videography in a single pellet reach-to-grasp task to characterize the neural circuits involved in the performance of skilled motor behavior in freely moving mice.

Fine motor skills are essential in everyday life and can be compromised in several nervous system disorders. The acquisition and performance of these ...

Neuroscience

Automated Assessment of Fine Motor Performance in Mice Using the Erasmus Ladder

Monitoring Fine and Associative Motor Learning in Mice Using the Erasmus Ladder

Behavior is shaped by actions, and actions necessitate motor skills such as strength, coordination, and learning. None of the behaviors essential for sustaining life would be possible without the ability to transition from one position to another. Unfortunately, motor skills can be compromised in a wide array of diseases. Therefore, investigating the mechanisms of motor functions at the cellular, molecular, and circuit levels, as well as understanding the symptoms, causes, and progression of motor disorders, is crucial for developing effective treatments. Mouse models are frequently employed for this purpose.
This article describes a protocol that allows the monitoring of various aspects of motor performance and learning in mice using an automated tool called the Erasmus Ladder. The assay involves two phases: an initial phase where mice are trained to navigate a horizontal ladder built of irregular rungs (&#34;fine motor learning&#34;), and a second phase where an obstacle is presented in the path of the moving animal. The perturbation can be unexpected (&#34;challenged motor learning&#34;) or preceded by an auditory tone (&#34;associative motor learning&#34;). The task is easy to conduct and is fully supported by automated software.
This report shows how different readouts from the test, when analyzed with sensitive statistical methods, allow fine monitoring of mouse motor skills using a small cohort of mice. We propose that the method will be highly sensitive to evaluate motor adaptations driven by environmental modifications as well as early-stage subtle motor deficits in mutant mice with compromised motor functions.

Author Spotlight: Unveiling Neural Mechanisms Through Automated Evaluation of Motor Learning and Myelin Plasticity Studies Using the Erasmus Ladder 

This article presents a protocol that allows a non-invasive and automated assessment of fine motor performance, as well as adaptive and associative motor learning upon challenges, using a device called the Erasmus Ladder. Task difficulty can be titrated to detect motor impairment ranging from major to subtle degrees.

Behavior is shaped by actions, and actions necessitate motor skills such as strength, coordination, and learning. None of the behaviors essential for ...

Evaluating Skilled Prehension in Mice Using an Auto-Trainer

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

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Automated Rat Single-Pellet Reaching with 3-Dimensional Reconstruction of Paw and Digit Trajectories

Behavioral Training Procedures for Head-fixed Virtual Reality in Mice

In Vivo Wireless Optogenetic Control of Skilled Motor Behavior

Monitoring Fine and Associative Motor Learning in Mice Using the Erasmus Ladder