The vermicelli handling test: a simple quantitative measure of dexterous forepaw function in rats

Abstract

Loss of function in the hands occurs with many brain disorders, but there are few measures of skillful forepaw use in rats available to model these impairments that are both sensitive and simple to administer. Whishaw and Coles previously described the dexterous manner in which rats manipulate food items with their paws, including thin pieces of pasta [Whishaw IQ, Coles BL. Varieties of paw and digit movement during spontaneous food handling in rats: postures, bimanual coordination, preferences, and the effect of forelimb cortex lesions. Behav Brain Res 1996;77:135-48]. We set out to develop a measure of this food handling behavior that would be quantitative, easy to administer, sensitive to the effects of damage to sensory and motor systems of the CNS and useful for identifying the side of lateralized impairments. When rats handle 7 cm lengths of vermicelli, they manipulate the pasta by repeatedly adjusting the forepaw hold on the pasta piece. As operationally defined, these adjustments can be easily identified and counted by an experimenter without specialized equipment. After unilateral sensorimotor cortex (SMC) lesions, transient middle cerebral artery occlusion (MCAO) and striatal dopamine depleting (6-hydroxydopamine, 6-OHDA) lesions in adult rats, there were enduring reductions in adjustments made with the contralateral forepaw. Additional pasta handling characteristics distinguished between the lesion types. MCAO and 6-OHDA lesions increased the frequency of several identified atypical handling patterns. Severe dopamine depletion increased eating time and adjustments made with the ipsilateral forepaw. However, contralateral forepaw adjustment number most sensitively detected enduring impairments across lesion types. Because of its ease of administration and sensitivity to lateralized impairments in skilled forepaw use, this measure may be useful in rat models of upper extremity impairment.

Figure 1

A trial in which the rat displays a typical handling pattern. A, The vermicelli piece is dropped into a conveniently viewed part of the cage. B, The rat begins eating using an asymmetrical holding pattern. The left and right paws in this example are designated as “grasp” and “guide” paws, respectively. C-D, The paws move together as the piece becomes shorter and digits become interposed.

Figure 2

Examples of adjustments. Each row is an example of the paw position before, during and after an adjustment. The adjusting paws are indicated by asterisks. A-C, Grasp-release-regrasp movements that reposition the paw on the pasta piece. D-E, Adjustments in which digits are partially extended and abducted followed by their flexion/adduction. In E, simultaneous adjustments in both paws are seen. Additional examples of adjustments can be found in supplementary material (VermiTutorial.ppt and VermiTrial.mov).

Figure 3

Atypical and sporadic behaviors. A, Paws together when long. This symmetrical paw position is more typical of shorter pasta pieces. B, Guide and grasp switch. The right paw (arrow) initiates eating in the grasp position and switches to the guide position. C, Failure to contact. The right paw (arrow) fails to contact the piece. D, Drop. The arrow indicates the dropped piece, E, Paws apart when short. The left paw would typically move next to the right when the piece is this short. The arrow indicates the end of the pasta piece. F, Mouth pulling. The piece is held in the mouth and pulled through the paws as they slide down. G, Abnormal posture. The pasta piece rests on the floor and the head is brought down to it as it is eaten. H, Iron grip and I, Guide around grasp. The grasp paw (arrow) is held in an iron grip, while the guide paw (as defined at the start of eating) moves around it. J, Angling with head tilt. The pasta piece is angled towards the intact body side as the head is tilted. The right paw is being held in an iron grip. The last three categories are characteristic of unilateral 6-OHDA lesions.

Figure 4

Representative coronal sections of A, an ischemic SMC lesion, B, an electrolytic SMC lesion and, C, a lesion resulting from MCAO. Numbers to the right are approximate coronal plane distances relative to bregma in mm. Scale bar = 1 mm

Figure 5

Ischemic SMC lesion effects on vermicelli handling. A, Adjustments made with the contralateral forepaw decreased compared to sham-operates and this endured throughout the 45 day post-lesion period of testing. Day 0 is the pre-operative time point. Electrolytic SMC lesions resulted in similar effects (see text for details). *P < 0.05 significantly different from sham. B, The magnitude of the post-lesion change in adjustments varied with endogenous asymmetries. Lesion effects in contralateral adjustments were less sensitively detected in rats that preferred to use the unimpaired forelimb for adjustments prior to the lesion (Ipsi Bias subgroup). † P < 0.05 significantly different from Contra/No Bias subgroup. C, Adjustments with the ipsilateral forelimb, time to eat and atypical behaviors were not significantly changed after the lesion.

Figure 6

MCAO effects on vermicelli handling. Lesions were made contralateral to the paw that was used most for adjustments in preoperative tests. A, Unilateral MCAO resulted in an enduring decrease in adjustments made with the contralateral forepaw. *P < 0.05, significantly different from Day 0. (Note the difference in scale compared with Fig. 5.) B, There were no significant changes in ipsilateral adjustment number or time to eat. C, Atypical behaviors were increased. This was significant relative to the preoperative time point at Day 2 (*P < 0.05). Data shown for Days 0, 5 and 28 are the average of 2 days, one collected in real time and the other from video playback (see text for details).

Figure 7

6-OHDA lesion effects on vermicelli handling. A, Both partial and severe dopamine depletions reduced contralateral adjustments compared with normals. After severe depletions, there was also a major increase in adjustments made with the ipsilateral forepaw. B, The time to eat was increased after severe depletions. C, Atypical behaviors were increased in both depletion groups. After severe depletion most increased were behavioral categories 8-10, iron grip, angling with head tilt and guide around grasp (see Fig. 3H-J). Error bars are for total atypical observation number (summed over categories 1-10). *P < 0.01 compared with normal.