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Peden-Asarch, A. M.

Publications and source records attributed to Peden-Asarch, A. M..

3 recordsLinked to original sources

Stars2Cells: Astrometric Tracking of Neurons Across Imaging Sessions

Chronic calcium imaging offers a window into how single neurons and ensemble activity change across days where identifying the same neurons from one session to the next is the prerequisite for answering questions regarding learning, drift, and plasticity over time. Yet only [~]2-3% of imaging laboratories publish longitudinal cross-session work, because existing registration tools depend on spatial-footprint or temporal correlations that degrade under repeated recording sessions. Here, we introduce Stars2Cells (S2C), a tracking pipeline inspired by astrometric plate-solving that represents each neurons local geometry as a four-dimensional quad descriptor invariant to rotation, translation, and uniform scaling. S2C operates purely on centroid coordinates and combines descriptor-space matching, Random Sample Consensus (RANSAC) verification, and Hungarian assignment. Across a synthetic benchmark of 1,262 paired runs spanning 100-1,000 neurons and 8 perturbation conditions plus 1 identity sanity-floor, S2C reached pooled F1 = 98.4% compared to the standard ROI-based matching of 36.0%. To show what this enables, we applied the pipeline to dorsomedial striatum (DMS) imaging during oral fentanyl behavioral-economics self-administration. Here, we show that a conserved population-rewarded lever press response in DMS masks near-complete single-neuron turnover. This representational-drift signature we demonstrated is invisible to the bulk photometry, and resolving it requires the same-cell tracking S2C provides. S2C is distributed as a GUI-driven standalone application for both macOS and Windows, requiring no Python, command line, or virtual environment setup.

neuroscience↗

Miniscope Processing Suite (MPS): An Intuitive, No-Code, Scalable Pipeline for Long Duration Calcium Imaging

Miniscope calcium imaging provides a unique window into the activity of neurons during behavior while enabling spatial localization of individual cells across time. Despite its potential to revolutionize in vivo imaging alongside the rise of optogenetic tools, miniscopes remain underutilized. This gap may stem from the lack of an easy-to-use preprocessing software tailored to miniscope data. To address this need, we developed the first no-code end-to-end scalable pipeline for preprocessing large miniscope recordings: the Miniscope Processing Suite (MPS). MPS is the first implementation of Constrained Non-negative Matrix Factorization (CNMF) with Nonnegative Double Singular Value Decomposition (NNDSVD) initialization, multi-lasso segmentation, and parallelized temporal and spatial updates, enabling analysis of recordings exceeding three hours on a standard hardware. We tested a large dataset consisting of 28 operant behavior sessions (77 hrs, 7.26 TB of video data) on a single workstation. MPS completed the analysis in 55.6 hrs, (averaging 0.72 minute of processing time per minute of recording), which is 10-20X faster than traditional pipelines. Packaged as an easy downloadable plug-and-play software with a graphical user interface and requiring no coding or Git experience, MPS lowers the barrier to miniscope analysis while improving on current methodologies.

neuroscience↗

Repeated fentanyl abstinence intensifies opioid withdrawal and induces a proinflammatory state in striatal microglia

Opioid withdrawal is a serious obstacle to self-initiated abstinence, and previous experiences of opioid withdrawal may exacerbate the severity of subsequent incidences. To study the impact of repeated opioid withdrawal episodes, we compared male and female mice after one or five cycles of fentanyl exposure and withdrawal. We selectively expressed hemagglutinin-tagged ribosomes (RiboTag) in microglia of transgenic mice to immunoprecipitate and sequence RNA actively undergoing translation (the "translatome") from striatal microglia during fentanyl withdrawal. Key changes were confirmed by RTqPCR of RiboTag RNA. Repeated bouts of fentanyl treatment and withdrawal impacted striatal microglia much more than a single cycle of fentanyl followed by withdrawal. Multiple withdrawal cycles reduced ramification of microglial processes, suggesting a more reactive cell state, and induced more severe behavioral withdrawal signs in mice. Five cycles of fentanyl exposure and withdrawal increased the expression of gene networks associated with innate immunity signaling. Indeed, 100% of the genes associated with the "microglia core sensome", were upregulated after five cycles of withdrawal. Together these results suggest that mouse striatal microglia initiate a proinflammatory response following five, but not one, opioid exposure and withdrawal experiences and suggest that drug therapies targeting microglial innate immune responses may mitigate the severe withdrawal associated with repeated opioid tolerance and withdrawal. Significance statementRepeated cycles of fentanyl administration and withdrawal caused worsened behavioral signs of withdrawal in mice. This is the first such study to directly examine the effects of repeated opioid withdrawal on mouse behavior. We also found that repeated opioid withdrawal increased the expression of RNAs related to the proinflammatory "microglia core sensome". Furthermore, microglia in the mouse striatum were present at a higher density with reduced ramification, which suggests that multiple opioid withdrawal experiences cause a significant change to microglial signaling-state.

neuroscience↗