Name: evaluating skilled prehension in mice using an auto-trainer
Uploaded: 2019-09-12T13:30:00
Description: Watch this Scientific Journal Video about Evaluating Skilled Prehension in Mice Using an Auto-Trainer at JoVE.com

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 d...

<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. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+automated+task+for+the+training+and+assessment+of+distal+forelimb+function+in+a+mouse+model+of+ischemic+stroke.">An automated task for the training and assessment of distal forelimb function in a mouse model of ischemic stroke.</a> Journal of Neuroscience Methods. 258, 16-23 (2016).</li><li>Bruinsma, B., 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=An+automated+home-cage-based+5-choice+serial+reaction+time+task+for+rapid+assessment+of+attention+and+impulsivity+in+rats.">An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats.</a> Psychopharmacology. , 1-12 (2019).</li><li>Francis, N. A., Kanold, P. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automated+operant+conditioning+in+the+mouse+home+cage.">Automated operant conditioning in the mouse home cage.</a> Frontiers in Neural Circuits. 11 (10), (2017).</li><li>Balcombe, J. P., Barnard, N. D., Sandusky, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Laboratory+routines+cause+animal+stress.">Laboratory routines cause animal stress.</a> Contemporary Topics in Laboratory Animal Science. 43, 42-51 (2004).</li><li>Fenrich, K. 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>

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.

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	<tbody>
		<tr height="19">
			<td height="19" style="height:19px;width:318px;">ABS Filament</td>
			<td style="width:242px;">Custom 3D Printed</td>
			<td style="width:166px;">N/A</td>
			<td style="width:595px;">utilized for pellet holder, frame, arm and funnel</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">ABS Sheet</td>
			<td>McMaster-Carr</td>
			<td>8586K581</td>
			<td>3/8&#34; thickness; used for platform compononents, positioning stand guides and base</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Adruino Mini</td>
			<td>Adruino</td>
			<td>A000087</td>
			<td>nano version also compatiable as well as other similar microcontrollers</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Bench-Top Adjustable-Height Positioning Stand</td>
			<td>McMaster-Carr</td>
			<td>9967T43</td>
			<td>35 lbs. load capacity</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Clear Acrylic Round Tube</td>
			<td>McMaster-Carr</td>
			<td>8532K14</td>
			<td>ID 3/8&#34;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Low-Carbon&#160;Steel Wire</td>
			<td>McMaster-Carr</td>
			<td>8855K14</td>
			<td>0.148&#34;&#160;diameter</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">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 height="19">
			<td height="19" style="height:19px;">Photointerrupter Breakout Board&#160;</td>
			<td>SparkFun</td>
			<td>BOB-09322 ROHS</td>
			<td>designed for Sharp GP1A57HRJ00F</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Reflective Object Sensor</td>
			<td>Fairchild Semiconductor</td>
			<td>QRD1113</td>
			<td>phototransistor output</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Servo Motor</td>
			<td>SparkFun</td>
			<td>S8213</td>
			<td>generic metal gear (micro size)</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">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 ...

Our technology automates a complicated behavioral analysis that can save time and serve as a springboard for many different types of studies. With our technique, the task and the reward are the same thing. There's no disconnect between performing a vague task, possibly incorrectly, and receiving a reward.Animal models provide an opportunity for testing approaches to augment recovery after a neurological injury. For example, in my lab we test approaches to augment recovery post-stroke, since there is an urgent need to develop innovative new approaches to post-stroke rehabilitation. In addition to stroke, our auto-trainer could be useful for studying motor learning before injury, as well as in models of Parkinson's, Alzheimer's, or traumatic brain injury.When a mouse reaches it's goal weight, start a training session by placing a 45 milligram pellet on the pellet surface directly in front of the slot, and allow the mouse to retrieve the pellet. When the mouse associates an open slot with being fed, use a pair of tweezers to hold a pellet in the same position that the mouse has retrieved the pellets previously. As the mouse begins to bite for the pellet, pull the pellet away approximately half a centimeter, such that the pellet is out of reach of the mouth.When the mouse extends a paw through the slot, reinforce the behavior by allowing the mouse to eat the pellet. While not instrumental to experimentation, record whether the left or right paw is preferred. As the mouse associates extending a paw with eating a pellet, further reinforce the behavior by withholding the pellet in response to attempts to retrieve the pellet with the mouth and tongue.Take care to stop your mice from successfully getting a pellet without using a paw, or they will learn bad habits that are hard to unlearn. Finalize the introduction of the desired paw-reaching behavior by placing the 45-milligram pellet just under one centimeter from the outer edge of the cage gate, such that the left or right-most point of the pellet is tangent to a line extending straight out from the edge of the cage gate slot. Then allow the mouse to attempt to retrieve the pellet, being vigilant to remove the pellet and prevent it's consumption if the mouse should attempt retrieval by some other method than paw extension.Before beginning the training session, click the Run arrow in the LabVIEW Interface of the auto-trainer and note the bait pellet sensor reading, both with and without a pellet in place. Click Stop to stop the test run and change the bait pellet sensor target to a value between those two readings. Place the modified mouse cage on the auto-trainer and affix the cage gate.Then align the pellet to the edge of the slot as in the manual procedure, and open a new training session in the LabVIEW Interface. Input the information as required to record data about the training session and click the Mouse ID field to enter the file name of each training session. Click the Total Pellets to Dispense During Routine field to control how many pellets are dispensed for a single experiment.Click the Pause After Pellet Number field to set a five second pause after the indicated pellet is removed from the diving board, and 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. Set the auto-trainer to manually record the distance at which the pellet is placed in the Reach Distance field, and click the Folder to Contain Logs field to select the file location to save the collected data. Once the information fields have been filled out, click Run 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.Once the software is set up, place the home cage of the mouse to be tested on the pedestal and click Run to allow the mouse to investigate the slot and it's new unfamiliar surroundings. Mice trained with the auto-trainer learned the prehension task and exhibit a clear increase in motor skill. This increase in skill is similar to that observed where the animal is trained manually without the use of the auto-trainer.Make sure to make the mice use their paws. If you let them think you're just letting them have food, they won't reach for you. An injury can be induced to any part of the motor pathway to determine what effects the lesion has on motor performance, and how to encourage recovery from said lesion.

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