The isometric pull task: A novel automated method for quantifying forelimb force generation in rats

Reach-to-grasp tasks are commonly used to assess forelimb function in rodent models. While these tasks have been useful for investigating several facets of forelimb function, they are typically labor-intensive and do not directly quantify physiological parameters. Here we describe the isometric pull task, a novel method to measure forelimb strength and function in rats. Animals were trained to reach outside the cage, grasp a handle attached to a stationary force transducer, and pull with a predetermined amount of force to receive a food reward. This task provides quantitative data on operant forelimb force generation. Multiple parameters can be measured with a high degree of accuracy, including force, success rate, pull attempts, and latency to maximal force. The task is fully automated, allowing a single experimenter to test multiple animals simultaneously with usually more than 300 trials per day, providing more statistical power than most other forelimb motor tasks. We demonstrate that an ischemic lesion in primary motor cortex yields robust deficits in all forelimb function parameters measured with this method. The isometric pull task is a significant advance in operant conditioning systems designed to automate the measurement of multiple facets of forelimb function and assess deficits in rodent models of brain damage and motor dysfunction.

[1]  I. Whishaw,et al.  Subcortical middle cerebral artery ischemia abolishes the digit flexion and closing used for grasping in rat skilled reaching , 2006, Neuroscience.

[2]  S. M. Michaelsen,et al.  Skilled forelimb reaching in Wistar rats: Evaluation by means of Montoya staircase test , 2009, Journal of Neuroscience Methods.

[3]  I. Whishaw,et al.  Complete Compensation in Skilled Reaching Success with Associated Impairments in Limb Synergies, after Dorsal Column Lesion in the Rat , 1999, The Journal of Neuroscience.

[4]  T. Schallert,et al.  CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury , 2000, Neuropharmacology.

[5]  Kelly A. Tennant,et al.  Sensorimotor behavioral effects of endothelin-1 induced small cortical infarcts in C57BL/6 mice , 2009, Journal of Neuroscience Methods.

[6]  Andreas R. Luft,et al.  Characterization of motor skill and instrumental learning time scales in a skilled reaching task in rat , 2004, Behavioural Brain Research.

[7]  Wolfram Tetzlaff,et al.  Proximal and distal impairments in rat forelimb use in reaching follow unilateral pyramidal tract lesions , 1993, Behavioural Brain Research.

[8]  J. Kleim,et al.  Functional reorganization of the rat motor cortex following motor skill learning. , 1998, Journal of neurophysiology.

[9]  S. Pellis,et al.  Analysis of limb use by control rats and unilateral DA-depleted rats in the Montoya staircase test: movements, impairments and compensatory strategies , 1997, Behavioural Brain Research.

[10]  Ian Q. Whishaw,et al.  Olfaction directs skilled forelimb reaching in the rat , 1989, Behavioural Brain Research.

[11]  S. Dunnett,et al.  A lateralised grip strength test to evaluate unilateral nigrostriatal lesions in rats , 1998, Neuroscience Letters.

[12]  S. Iversen,et al.  The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke , 2004, Behavioural Brain Research.

[13]  S. Barbay,et al.  Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. , 2003, Journal of neurophysiology.

[14]  I. Whishaw,et al.  No improvement by amphetamine on learned non‐use, attempts, success or movement in skilled reaching by the rat after motor cortex stroke , 2007, The European journal of neuroscience.

[15]  Ian Q Whishaw,et al.  Skilled reaching an action pattern: stability in rat (Rattus norvegicus) grasping movements as a function of changing food pellet size , 2000, Behavioural Brain Research.

[16]  I. Whishaw,et al.  Parallel stages of learning and recovery of skilled reaching after motor cortex stroke: “Oppositions” organize normal and compensatory movements , 2006, Behavioural Brain Research.

[17]  S. Dunnett,et al.  The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats , 1991, Journal of Neuroscience Methods.

[18]  T. Jones,et al.  Cortical electrical stimulation combined with rehabilitative training: Enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats , 2003, Neurological research.

[19]  I. Whishaw,et al.  Skilled reaching impairments from the lateral frontal cortex component of middle cerebral artery stroke: a qualitative and quantitative comparison to focal motor cortex lesions in rats , 2005, Behavioural Brain Research.

[20]  Peter D. Neilson,et al.  The nature of the loss of strength and dexterity in the upper limb following stroke , 1996 .

[21]  I. Whishaw,et al.  Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6‐OHDA dopamine‐depleted (hemi‐Parkinson analogue) rats , 2001, The European journal of neuroscience.

[22]  T. Jones,et al.  Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats , 2007, Behavioural Brain Research.

[23]  T. Jones,et al.  d-Amphetamine enhances skilled reaching after ischemic cortical lesions in rats , 2005, Neuroscience Letters.

[24]  J. Faraji,et al.  Sequential bilateral striatal lesions have additive effects on single skilled limb use in rats , 2007, Behavioural Brain Research.

[25]  J. Kleim,et al.  Sensitivity of cortical movement representations to motor experience: evidence that skill learning but not strength training induces cortical reorganization , 2001, Behavioural Brain Research.

[26]  Ian Q. Whishaw,et al.  The structure of skilled forelimb reaching in the rat: A proximally driven movement with a single distal rotatory component , 1990, Behavioural Brain Research.

[27]  Ian Q. Whishaw,et al.  The impairments in reaching and the movements of compensation in rats with motor cortex lesions: an endpoint, videorecording, and movement notation analysis , 1991, Behavioural Brain Research.

[28]  M. Kilgard,et al.  Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. , 2012, Cerebral cortex.

[29]  R. Mandler,et al.  Quantitative measurement of muscle strength in the mouse , 1995, Journal of Neuroscience Methods.

[30]  F. Colbourne,et al.  Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats , 2006, Behavioural Brain Research.

[31]  L. Ada,et al.  Slowness to develop force contributes to weakness after stroke. , 1999, Archives of Physical Medicine and Rehabilitation.

[32]  S. Barbay,et al.  Combination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery After a Focal Cortical Infarct in Rats , 2010, Stroke.

[33]  Ian Q Whishaw,et al.  The pasta matrix reaching task: a simple test for measuring skilled reaching distance, direction, and dexterity in rats , 2001, Journal of Neuroscience Methods.