Towards elucidation of circuit mechanisms for feeding-related manual dexterity

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PROJECT SUMMARY Dexterous food-handling is a critical but still poorly understood type of basic motor behavior. We propose an exploratory research program to investigate how the mouse uses its digits and forepaws to dexterously handle food. Preliminary results suggest that mouse food-handling movements, despite appearing extremely complex, can be decomposed into several types of simpler elements, tentatively identified as distinct and very rapid submovements that exhibit partly stereotyped and partly variable kinematic features. They also suggest that the mouse’s thumb (first digit, or D1; pollex) plays a surprisingly large and previously unrecognized role in dexterous food-handling. To explore these hypotheses and observations, we will first develop an approach for quantitatively characterizing seed-handling behaviors of freely moving mice. For this we will use high-speed, close-up video capture, combined with deep neural network methods for automated markerless tracking (DeepLabCut). We will then develop a novel trial-based paradigm for characterizing seed-handling under the more experimentally controlled conditions of head-fixation. We will combine this approach with tools for optogenetic silencing of either selectively targeted cortical areas or selectively labeled corticospinal neurons in motor cortex, as well as multi- probe/multi-channel linear array recordings of spiking activity in key nodes along sensorimotor pathways. Collectively this work will advance our understanding of the elemental movements involved in the dexterous manipulation of food, providing new insights into this process in a genetically tractable model organism, and opening the way for future studies to dissect the cellular mechanisms in sensorimotor circuits mediating specific aspects of forelimb and digit motor control.