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

Abstract

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 ± 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.

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

“…We next asked whether the motor cortex in the left or right hemisphere exerts control of the impaired forepaw, since each motor cortex is the origin of one of the two pathways for motor control we considered (Figure 1 ). To assay forepaw control, we used the knob supination task (Meyers et al, 2016 ; Butensky et al, 2017 ; Sindhurakar et al, 2017 ); which was titrated to the maximum level achievable by rats with neonatal pyramidotomy (60° from pronation to supination). We then titrated the concentration of muscimol that was used for cortical inactivation to cause a significant deficit in the contralateral forelimb in uninjured adult rats.…”

“…In the knob supination task, adult rats with neonatal pyramidotomy ( n = 7) and control rats ( n = 5) were placed into a reaching box for reaching, grasping, and supinating a knob to receive a food reward (Meyers et al, 2016 ; Butensky et al, 2017 ; Sindhurakar et al, 2017 ). All rats were trained to supinate with their right forepaw for 3–4 weeks until they were able to turn the knob 60° at a success rate of 70% or more.…”

Automated Forelimb Tasks for Rodents: Current Advantages and Limitations, and Future Promise

“…Adaptive training protocols can be designed to vary difficulty of the task automatically based on how animals perform. For instance, when training animals on tasks that require them to manipulate a target mounted on a sensor, 9,28 a computer algorithm can adjust the criterion for task success based on the animals’ performance. The software computes the success rate of the 10 most recent trials and automatically either increases or decreases the difficulty of the task.…”

“…One example of such a task is the knob supination task ( Figure 3) that was designed to specifically measure distal forelimb supination in rodents. 9,28,36 Supination loss is a relatively specific sign of injury to the descending motor circuits. 37 In addition to being a sensitive sign of motor circuit impairment, supination loss strongly correlates with loss of hand function.…”

“…For example, the knob task can measure angle changes as small as one-fourth of a degree, and position is sampled at 100 Hz. 9,28,36 The ability to measure movements at such high resolution is a theoretical advantage at this time because of lack of head-to-head comparisons with manual assessment of movement kinetics.…”