A novel biomechanical model of the mouse forelimb predicts muscle activity in optimal control simulations of reaching movements

Abstract

ABSTRACTMice are key model organisms in genetics, neuroscience and motor systems physiology. Fine motor control tasks performed by mice have become widely used in assaying neural and biophysical motor system mechanisms, including lever or joystick manipulation, and reach-to-grasp tasks (Becker et al., 2019; Bollu et al., 2019; Conner at al., 2021). Although fine motor tasks provide useful insights into behaviors which require complex multi-joint motor control, there is no previously developed physiological biomechanical model of the adult mouse forelimb available for estimating kinematics (including joint angles, joint velocities, fiber lengths and fiber velocities) nor muscle activity or kinetics (including forces and moments) during these behaviors. Here we have developed a musculoskeletal model based on high-resolution imaging and reconstruction of the mouse forelimb that includes muscles spanning the neck, trunk, shoulder, and limbs using anatomical data. Physics-based optimal control simulations of the forelimb model were used to estimatein vivomuscle activity present when constrained to the tracked kinematics during mouse reaching movements. The activity of a subset of muscles was recorded via electromyography and used as the ground truth to assess the accuracy of the muscle patterning in simulation. We found that the synthesized muscle patterning in the forelimb model had a strong resemblance to empirical muscle patterning, suggesting that our model has utility in providing a realistic set of estimated muscle excitations over time when provided with a kinematic template. The strength of the resemblance between empirical muscle activity and optimal control predictions increases as mice performance improves throughout learning of the reaching task. Our computational tools are available as open-source in the OpenSim physics and modeling platform (Seth et al., 2018). Our model can enhance research into limb control across broad research topics and can inform analyses of motor learning, muscle synergies, neural patterning, and behavioral research that would otherwise be inaccessible.