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Development of a skilled forelimb reach task in mice and the effects of C-8 projecting cortical spinal neuron ablation in motor learning by photothermal Au nanoparticles
Abstract
Motor learning is measured quantitatively through many behavioral tests. Behavioral models for motor learning observe skill acquisition and performance over a period of time within rodents. One such behavioral test is the skilled forelimb reach-to-grasp test. This skilled forelimb reach-to-grasp test has been extensively used to observe motor learning in behavioral studies and is an appropriate metric that can be used to asses experiments of the motor cortex. In this study, the skilled forelimb reach-to-grasp task was developed in young adult mice to measure motor skills as a function of learning. The skilled forelimb reach task was developed to consistently tease out the rapid learning phase of learning in adult mice and was further characterized for future studies. In this study, the skilled forelimb reach task was corroborated that age and gender do not significantly affect the degree of learning between groups. However, the amount of time spent during handling and conditioning mice play a significant role in capturing the steep learning curve characterized as the rapid learning phase. In this study, 50 trials per training session was found to be a significant number of trials that allowed motor learning to occur whereas 30 trials of skilled forelimb reaching was not. Layer V cortical spinal neurons project to the eighth cervical segment of the spinal cord (C8) and synapse onto interneurons that control the movements of the digits. Multifunctional gold rod nanoparticles (nanorods) possess the ability to transform photoenergy into thermal energy. Using CTB peptides conjugated to the gold nanorods for retrograde transport, these C8 projecting neurons were tagged with these photothermal golden nanorods and ablated by the heat generated by the golden nanoparticles. Ablation of these C8 projecting layer V cortical spinal neurons after seven days of training did not result in a significant deficit of motor performance skilled forelimb reach task the day after the neurons were ablated. After more time had passed after the ablation, motor performance returned to levels prior to the ablation and post training day 5. We could not draw any conclusions in this study if ablation of layer V cortical spinal neurons prior to training in the skilled forelimb reach task resulted in a decreased degree of motor learning. The learning curve of mice exposed to the 760nm laser did not experience as much of steep learning curve that was observed in mice that did not receive 760nm light exposure. Other types of neural plasticity are at play that may compensate for the elimination of neurons that have been suggested to play a key role in motor learning