Cortical control of forelimb and lingual kinematic primitives in mice
Bollu, Teja Pratap
Motor sequences are constructed from primitives, hypothesized building blocks of movement, but mechanisms of primitive generation remain unclear. To dissect the neural circuits underlying generation of movement primitives, I designed two behavioral paradigms for mice. First, using a novel forelimb sensor, I trained freely-moving mice to initiate forelimb sequences with clearly resolved submillimeter-scale micromovements followed by millimeter-scale reaches to learned spatial targets. Hundreds of thousands of trajectories were decomposed into millions of kinematic primitives, while closed-loop photoinhibition was used to test roles of motor cortical areas. Second, I imaged the mouse tongue at 1kHz during a cued directional lick task, and using a novel deep-learning based artificial neural network for semantic segmentation we resolved tens of thousands of mouse tongue trajectories with a precision of ~60um. Cue-evoked licks exhibited previously unobserved fine-scale movements which, like a hand searching for an unseen object, were produced after misses and were directionally biased towards remembered locations. Photoinhibition of contralateral “forelimb” motor cortex (CFA) during the forelimb task and bilateral “tongue” motor cortex (ALM) in a directional licking task led to both shared and distinct phenotypes. Inactivations reduced peak speed and pathlengths of primitives in both tongue and forelimb trajectories. However, while CFA inactivations did not substantially affect primitive direction, termination, or complexity, resulting in isomorphic, spatially contracted forelimb trajectories. ALM inactivations specifically abolished the fine-scale adjustments in the tongue trajectories, reducing the complexity of movements. These findings identify conditions where loss of motor cortical drive leads to distinct behavioral deficits. The combination of high precision forelimb and tongue kinematics with automated training and neural manipulation provides a system for studying how motor sequences are constructed from elemental building blocks.
Fetcho, Joseph; Cohen, Itai; Warden, Melissa
Neurobiology and Behavior
Ph. D., Neurobiology and Behavior
Doctor of Philosophy
dissertation or thesis