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Sriworarat, C.

Publications and source records attributed to Sriworarat, C..

6 recordsLinked to original sources

Multi-sample non-negative spatial factorization

Analyzing multi-sample spatial transcriptomics data requires accounting for biological variation. We present multi-sample non-negative spatial factorization (mNSF), an alignment-free framework extending single-sample spatial factorization (NSF) to multi-sample datasets. mNSF incorporates sample-specific spatial correlation modeling and extracts low-dimensional data representations. Through simulations and real data analysis, we demonstrate mNSFs efficacy in identifying true factors, shared anatomical regions, and region-specific biological functions. mNSFs performance is comparable to alignment-based methods when alignment is feasible, while enabling analysis in scenarios where spatial alignment is unfeasible. mNSF shows promise as a robust method for analyzing spatially resolved transcriptomics data across multiple samples.

genomics↗

Integrated single cell and unsupervised spatial transcriptomic analysis defines molecular anatomy of the human dorsolateral prefrontal cortex

The molecular organization of the human neocortex has been historically studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally-defined spatial domains that move beyond classic cytoarchitecture. Here we used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex (DLPFC). Integration with paired single nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we map the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains. Finally, we provide resources for the scientific community to explore these integrated spatial and single cell datasets at research.libd.org/spatialDLPFC/. SummaryGeneration of a molecular neuroanatomical map of the human prefrontal cortex reveals novel spatial domains and cell-cell interactions relevant for psychiatric disease.

neuroscience↗

Performant web-based interactive visualization tool for spatially-resolved transcriptomics experiments

High-resolution and multiplexed imaging techniques are giving us an increasingly detailed observation of a biological system. However, sharing, exploring, and customizing the visualization of large multidimensional images can be a challenge. Here, we introduce Samui, a performant and interactive image visualization tool that runs completely in the web browser. Samui is specifically designed for fast image visualization and annotation and enables users to browse through large images and their selected features within seconds of receiving a link. We demonstrate the broad utility of Samui with images generated with two platforms: Vizgen MERFISH and 10x Genomics Visium Spatial Gene Expression. Samui along with example datasets is available at https://samuibrowser.com.

bioinformatics↗

Excitatory synaptogenesis in the anterior cingulate cortex is required for effort/reward evaluation

Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant-conditioning via lever-press for food reward-training in mice induces excitatory synapse formation onto a subset of Anterior Cingulate Cortex neurons projecting to the dorsomedial striatum (ACC->DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor 2{delta}-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of 2{delta}-1 in the adult ACC->DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation did not impact learning but instead resulted in a profound increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC->DMS neurons rescued or phenocopied the behaviors of the 2{delta}-1 cKO mice highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.

neuroscience↗

improv: A flexible software platform for adaptive neuroscience experiments

Current neuroscience research is often limited to testing predetermined hypotheses and post hoc analysis of already collected data. Adaptive experimental designs, in which modeling drives ongoing data collection and selects experimental manipulations, offer a promising alternative. Still, tight integration between models and data collection requires coordinating diverse hardware configurations and complex computations under real-time constraints. Here, we introduce improv, a software platform that allows users to fully integrate custom modeling, analysis, and visualization with data collection and experimental control. We demonstrate both in silico and in vivo how improv enables more efficient experimental designs for discovery and validation across various model organisms and data types. Improv can orchestrate custom real-time behavioral analyses, rapid functional typing of neural responses from large populations via calcium microscopy, and optimal visual stimulus selection. We incorporate real-time machine learning methods for dimension reduction and predictive modeling of latent neural and behavioral features. Finally, we demonstrate how improv can perform model-driven interactive imaging and simultaneous optogenetic photostimulation of visually responsive neurons in the larval zebrafish brain expressing GCaMP6s and the red-shifted opsin rsChRmine. Together, these results demonstrate the power of improv to integrate modeling with data collection and experimental control to achieve next-generation adaptive experiments.

neuroscience↗

Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males

Gestational exposure to environmental toxins and socioeconomic stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism. We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated the maternal immune system. Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Genetic ablation of microglia during the same critical period mimicked the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development.

neuroscience↗