Browsing by Author "Mi, Xuelong"

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    Brain Signal Quantification and Functional Unit Analysis in Fluorescent Imaging Data by Unsupervised Learning
    Mi, Xuelong (Virginia Tech, 2024-06-04)
    Optical recording of various brain signals is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. A major challenge in leveraging the technique is to identify and quantify the rich patterns embedded in the data. However, existing methods often struggle, either due to their limited signal analysis capabilities or poor performance. Here we present Activity Quantification and Analysis (AQuA2), an innovative analysis platform built upon machine learning theory. AQuA2 features a novel event detection pipeline for precise quantification of intricate brain signals and incorporates a Consensus Functional Unit (CFU) module to explore interactions among potential functional units driving repetitive signals. To enhance efficiency, we developed BIdirectional pushing with Linear Component Operations (BILCO) algorithm to handle propagation analysis, a time-consuming step using traditional algorithms. Furthermore, considering user-friendliness, AQuA2 is implemented as both a MATLAB package and a Fiji plugin, complete with a graphical interface for enhanced usability. AQuA2's validation through both simulation and real-world applications demonstrates its superior performance compared to its peers. Applied across various sensors (Calcium, NE, and ATP), cell types (astrocytes, oligodendrocytes, and neurons), animal models (zebrafish and mouse), and imaging modalities (two-photon, light sheet, and confocal), AQuA2 consistently delivers promising results and novel insights, showcasing its versatility in fluorescent imaging data analysis.
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    Norepinephrine links astrocytic activity to regulation of cortical state
    Reitman, Michael E.; Tse, Vincent; Mi, Xuelong; Willoughby, Drew D.; Peinado, Alba; Aivazidis, Alexander; Myagmar, Bat-Erdene; Simpson, Paul C.; Bayraktar, Omer A.; Yu, Guoqiang; Poskanzer, Kira E. (Nature Portfolio, 2023-04)
    Cortical state, defined by population-level neuronal activity patterns, determines sensory perception. While arousal-associated neuromodulators-including norepinephrine (NE)-reduce cortical synchrony, how the cortex resynchronizes remains unknown. Furthermore, general mechanisms regulating cortical synchrony in the wake state are poorly understood. Using in vivo imaging and electrophysiology in mouse visual cortex, we describe a critical role for cortical astrocytes in circuit resynchronization. We characterize astrocytes' calcium responses to changes in behavioral arousal and NE, and show that astrocytes signal when arousal-driven neuronal activity is reduced and bi-hemispheric cortical synchrony is increased. Using in vivo pharmacology, we uncover a paradoxical, synchronizing response to Adra1a receptor stimulation. We reconcile these results by demonstrating that astrocyte-specific deletion of Adra1a enhances arousal-driven neuronal activity, while impairing arousal-related cortical synchrony. Our findings demonstrate that astrocytic NE signaling acts as a distinct neuromodulatory pathway, regulating cortical state and linking arousal-associated desynchrony to cortical circuit resynchronization. The authors show that norepinephrine signaling to astrocytes in the mouse visual cortex acts as a separate neuromodulatory pathway that regulates the effects of arousal on neuronal activity and cortical state.