Mammalian cortex has both local and cross-area connections, suggesting vital roles for both local and cross-area neural population dynamics in cortically-dependent tasks, like movement learning. Prior studies of movement learning have focused on how single-area population dynamics change during short-term adaptation. It is unclear how cross-area dynamics contribute to movement learning, particularly long-term learning and skill acquisition. Using simultaneous recordings of rodent motor (M1) and premotor (M2) cortex and computational methods, we show how cross-area activity patterns evolve during reach-to-grasp learning in rats. The emergence of reach-related modulation in cross-area activity correlates with skill acquisition, and single-trial modulation in cross-area activity predicts reaction time and reach duration. Local M2 neural activity precedes local M1 activity, supporting top-down hierarchy between the regions. M2 inactivation preferentially affects cross-area dynamics and behavior, with minimal disruption of local M1 dynamics. Together, these results indicate that cross-area population dynamics are necessary for learned motor skills.
The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic β-cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic β-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold-free formation of densely packed β-cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the β-cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the β-cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species-induced caspase-mediated pathway. The β-cells' MAP might provide a potential new map in the pathophysiological mechanisms of β cells.
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