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Nguyen, A.-T.

Publications and source records attributed to Nguyen, A.-T..

2 recordsLinked to original sources

Differential Glutamatergic Inputs to Semilunar Granule Cells and Granule Cells Underscore Dentate Gyrus Projection Neuron Diversity

Semilunar Granule Cells (SGCs) are sparse dentate gyrus projection neurons whose role in the dentate circuit, including pathway specific inputs, remains unknown. We report that SGCs receive more frequent spontaneous excitatory synaptic inputs than granule cells (GCs). Dual GC-SGC recordings identified that SGCs receive stronger medial entorhinal cortex and associational synaptic drive but lack short-term facilitation of lateral entorhinal cortex inputs observed in GCs. SGCs dendritic spine density in proximal and middle dendrites was greater than in GCs. However, the strength of commissural inputs and dendritic input integration, examined in passive morphometric simulations, were not different between cell types. Activity dependent labeling identified an overrepresentation of SGCs among neuronal ensembles in both mice trained in a spatial memory task and task naive controls. The divergence of modality specific inputs to SGCs and GCs can enable parallel processing of information streams and expand the computational capacity of the dentate gyrus.

neuroscience↗

Fluorogenic Aptamer Optimizations on a Massively Parallel Sequencing Platform

Fluorogenic aptamers (FAPs) have become an increasingly important tool in cellular sensing and pathogen diagnostics. However, fine-tuning FAPs for enhanced performance remains challenging even with the structural details provided by X-ray crystallography. Here we present a novel approach to optimize a DNA-based FAP (D-FAP), Lettuce, on repurposed Illumina next-generation sequencing (NGS) chips. When substituting its cognate chromophore, DFHBI-1T, with TO1-biotin, Lettuce not only shows a red-shifted emission peak by 53 nm (from 505 to 558 nm), but also a 4-fold bulk fluorescence enhancement. After screening 8,821 Lettuce variants complexed with TO1-biotin, the C14T mutation is found to exhibit an improved apparent dissociated constant ([Formula] vs. 0.82 {micro}M), an increased quantum yield (QY: 0.62 vs. 0.59) and an elongated fluorescence lifetime ({tau}: 6.00 vs. 5.77 ns), giving 45% more ensemble fluorescence than the canonical Lettuce/TO1-biotin complex. Molecular dynamic simulations further indicate that the {pi}-{pi} stacking interaction is key to determining the coordination structure of TO1-biotin in Lettuce. Our screening-and-simulation pipeline can effectively optimize FAPs without any prior structural knowledge of the canonical FAP/chromophore complexes, providing not only improved molecular probes for fluorescence sensing but also insights into aptamer-chromophore interactions.

biophysics↗