Name: compensatory limb use and behavioral assessment of motor skill learning following sensorimotor cortex injury in a mouse model of ischemic stroke
Uploaded: 2014-07-10T14:00:00
Description: Watch this Scientific Journal Video about Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke Video at JoVE

The authors would like to thank Theresa Jones, Ph.D. for her guidance and assistance in adapting the reaching task to mice. Data presented in this manuscript were supported by grants from NIH-NINDS (NS64586 to TAJ and NS076275 to ALK) and a predoctoral NRSA to KAT (F31AG034032). The NIH was not involved in any aspect of study designs or analyses presented in this manuscript nor in the composition of this manuscript.

The following methods are in accordance with protocols approved by the University of Texas at Austin and Illinois Wesleyan Animal Care and Use Committees.&#160;It is recommended that researchers either wear gloves or take appropriate precautions (washing hands before and after) when engaging in behavioral training with any laboratory animal. Gloves must be worn when handling animals in preparation for and during surgery.
1. Habituation and Food Restriction
NOTE: As th...

<ol>
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The PMRT represents a simple, quantitative way to assess skilled reaching performance in mice. Though time consuming, it is possible for previously inexperienced undergraduates to be trained to collect reliable and reproducible data with only a few training sessions. The task is sensitive enough to measure even slight changes in mouse motor skill performance following ischemic insult 3, 13, 15, and a number of studies cite long-term deficits with a variety of training protocols 15, 20, 22. Because i...

Mouse models have become increasingly popular for experimental stroke research due in part to their convenience and affordability, as well as the availability of transgenic lines that are suitable for in vivo imaging among other applications. With this increased popularity in experimental models, the interest in developing sensitive behavioral assessments of functional outcome following injury has also increased 1-7. The development of animal training protocols that mimic both rehabilitation and compensatory strategies used by human stroke survivors improves the ability to successfully translate findings from experimental animal studies to use in the clinic 8. Motor skill training on the Pasta Matrix Reaching Task (PMRT) has been previously established as a sensitive behavioral assessment of motor skill outcome following ischemic insult of the sensorimotor cortex 3.
One of the primary interests in stroke research concerns rehabilitation and the development and understanding of behavioral strategies that promote improved recovery of function following insult. Currently, rehabilitation strategies in humans result in incomplete recovery 8. In addition, rehabilitation therapists must combat compensatory strategies that stroke survivors develop during recovery that may undermine their ability to fully regain function of their affected limb(s). For example, following a unilateral stroke that affects upper extremity function, humans tend to develop a reliance on their less-affected limb 9, 10. While improving a person&#8217;s ability to function in the short term, this learned non-use of the affected limb may impede its ultimate recovery potential, as demonstrated in animal models 11-13. These findings in animals have helped to inform the development and use of constraint-induced movement therapy in humans 14. Animal models are beneficial for improving rehabilitation strategies by allowing researchers to explore the neurobiological mechanisms that subserve and promote recovery of function. In addition to being an effective behavioral assessment of post-stroke function, the PMRT has been established as an effective rehabilitative strategy to promote improved functional outcome following sensorimotor stroke 15. The PMRT can also be used to effectively mimic learned non-use of the affected limb and therefore offer insight into behavioral manipulations that may improve functional recovery despite initial over-reliance on the less-affected limb 13.
Construction of the PMRT has been described previously 3. Briefly, the reaching chamber is composed of four Plexiglas walls (20 cm tall, 15 cm long, and 8.5 cm wide) with an open top and bottom. There is a center slit (13 cm tall and 5 mm wide) extending from the bottom base of the front wall of the chamber that serves as the reaching aperture (Figure 1A). The pasta matrix is a heavy-duty plastic block (8.5 cm long, 5 cm wide, and 1.5 cm tall) with 1 mm diameter holes drilled completely through the depth of the block. There are a total of 260 holes, beginning 2 mm from the reaching window with 2 mm between each hole (Figure 1B). The pasta matrix is designed such that dry, vertically oriented pasta pieces extend through the entire depth of the matrix stage with approximately half of the pasta piece exposed. A removable piece of overhead plastic or cardstock should be cut to size and taped securely to the underside of the matrix. This prevents the pasta pieces from falling out of the matrix during transport and allows for easy removal of broken pasta pieces.
The PMRT is a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic clinical phenomena. As a behavioral outcome measure, the PMRT allows experimenters to collect behavioral data that more accurately reflect the effectiveness of a rehabilitative strategy than does the traditional measure of infarct size 3, 16. As a behavioral manipulation, the PMRT allows experimenters to control upper limb use in mice in order to mimic clinical experiences of rehabilitation (i.e. affected limb training) or learned non-use (i.e. less-affected limb training). When combined with neuroanatomical methods, the PMRT provides researchers with an opportunity to explore the mechanisms that support behavioral recovery of function or maladaptive plasticity following compensatory limb use after stroke. The PMRT could be further applied to other murine models of brain injury and upper extremity impairment, such as traumatic brain injury. Another advantage of the PMRT is its affordability. The equipment required for the task can be constructed fairly reasonably in house, data collection does not require a large amount of space or financial resources, and the task is simple enough for undergraduate students to reliably collect data. Further, the PMRT is sensitive to even small behavioral deficits 3, 13. This protocol provides a simple and effective way to assess motor skill learning, promote behavioral recovery following injury, and mimic learned non-use phenomena in an established murine model of stroke.

<table border="0" cellpadding="0" cellspacing="0" width="794">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:71px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:388px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Reaching Chamber</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td>Reaching chambers are made in house with Plexiglas</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Pasta Matrix Block</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td>The Pasta Matrix box is made in house using a heavy plastic block</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Capellini Pasta</td>
			<td style="width:71px;">DeCecco</td>
			<td style="width:119px;"></td>
			<td style="width:388px;">DeCecco brand capellini pasta can be purchased in a grocery store or through an online retailer such as Amazon</td>
		</tr>
	</tbody>
</table>

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.

The results from PMRT analysis should include the number of pasta pieces broken and the pattern of successful reaches. Results from mice with sensorimotor cortical lesions indicate that ischemic insult affects both the number of successful reaches as well as physical reach patterns 3, 19, as demonstrated in Figure 3A. Representative pattern changes can be observed in Figure 3B. The ability of the PMRT to mimic learned non-use effects in mice is demonstrated by impaired recover...

Watch this Scientific Journal Video about Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke Video at JoVE

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

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.

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 ...

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Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of ...

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach Video (Video) | JoVE

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

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

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning Video (Video) | JoVE

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

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning Video (Video) | JoVE

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Investigating Motor Skill Learning Processes with a Robotic Manipulandum Video (Video) | JoVE

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

Using a Split-belt Treadmill to Evaluate Generalization of Human Locomotor Adaptation

Using a Split-belt Treadmill to Evaluate Generalization of Human Locomotor Adaptation Video (Video) | JoVE

Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. ...

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury Video (Video) | JoVE

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

The "Motor" in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task

The "Motor" in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task Video (Video) | JoVE

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that ...