Biology subjects

Do, Q.

Publications and source records attributed to Do, Q..

8 recordsLinked to original sources

bioRxiv2026

Diurnal rhythms of choice: a novel state-dependent drift diffusion model uncovers time-dependent changes in rat decision making

2Time-of-day severely impacts human decision-making, with real-world consequences. Studying shifts in decision-making strategy requires controlled, long timescale behavioral measurement and analyses that can extract insight from time-varying behavior. We introduce two complementary advances to address this gap: an autonomous 24-hour training facility for continuous behavioral measurement during decision-making and an interpretable modeling framework that captures non-stationary decision dynamics from reaction times and choices. Rats were trained on a visual evidence accumulation task across months, generating over a half million trials spanning the circadian period. Our model revealed latent behavioral states characterized by distinct evidence accumulation parameters, including differences in drift rate, bias, and decision-commitment time. These states recur across days and align with feeding schedules and the light-dark cycle, producing periodic fluctuations in performance over 24 hours. Together, these results demonstrate how continuous behavioral sampling combined with generative modeling uncovers long-timescale structure in decision-making obscured by stationary analyses. 1 HIGHLIGHTSO_LI24-hour live-in operant system allows autonomous training in cognitive tasks across months C_LIO_LI24-hour measurements reveal that rat performance fluctuates with time of day C_LIO_LINovel DDM-HMM framework identifies reaction time and accuracy shifts across multiple timescales C_LIO_LIDDM-HMM captures serial dependence in decisions that classic models ignore C_LI

animal behavior and cognition↗

bioRxiv2025

Altered perceptual integration and learning in autism revealed by games inspired by rodent operant tasks

Altered perception is a key feature of autism spectrum disorder (ASD), yet its precise nature and variability across individuals remain unclear. We developed an online video game, inspired by rodent operant tasks, to assess visual evidence integration. The game employs nonverbal, reward-based training and a pulsed stimulus design for precise control of sensory input, enabling detailed individual-level behavioral analysis. It was playable by typically developing adolescents and their autistic siblings, who spanned the spectrum, including those with profound autism. Game performance correlated with standard ASD survey scores, with ASD participants exhibiting slower learning and altered perceptual integration. Behavioral data were well fit by computational models in which perceptual and learning deficits in ASD arose from increased noise in higher- order visual processing. Our findings reveal that deficits in perceptual integration are widespread across ASD, correlate with symptom severity in social and adaptive domains, and may arise from instability of sensory representations.

neuroscience↗

bioRxiv2024

A cross-species framework for investigating perceptual evidence accumulation

Cross-species studies are important for a comprehensive understanding of brain functions. However, direct quantitative comparison of behaviors across species presents a significant challenge. To enable such comparisons in perceptual decision-making, we developed a synchronized evidence accumulation task for human and non-human animals, by aligning mechanics, stimuli, and training. The task was readily learned by rats, mice and humans, with each species exhibiting qualitatively similar performance. Quantitative model comparison revealed that all three species employed an evidence accumulation strategy, but differed in speed, accuracy, and key decision parameters. Human performance prioritized accuracy, whereas rodent performance was limited by internal time-pressure. Rats optimized reward rate, while mice appeared to switch between evidence accumulation and other strategies trial-to-trial. Together, these results reveal striking similarities and species-specific priorities in decision-making. Furthermore, the synchronized behavioral framework we present may facilitate future studies involving cross-species comparisons, such as evaluating the face validity of animal models of neuropsychiatric disorders. HighlightsO_LIDevelopment of an evidence accumulation task for rats and mice C_LIO_LISynchronized video game allows direct comparisons with humans C_LIO_LIRat, mouse and human behavior are well fit by the same decision models C_LIO_LIModel parameters reveal species-specific priorities in accumulation strategy C_LI

animal behavior and cognition↗

bioRxiv2023

A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy

In our brains, different neurons make appropriate connections; however, there remain few in vitro models of such circuits. We use an open microfluidic approach to build and study neuronal circuits in vitro in ways that fit easily into existing bio-medical workflows. Dumbbell-shaped circuits are built in minutes in standard Petri dishes; the aqueous phase is confined by fluid walls - interfaces between cell-growth medium and an immiscible fluorocarbon, FC40. Conditions are established that ensure post-mitotic neurons derived from human induced pluripotent stem cells (iPSCs) plated in one chamber of a dumbbell remain where deposited. After seeding cortical neurons on one side, axons grow through the connecting conduit to ramify amongst striatal neurons on the other - an arrangement mimicking unidirectional cortico-striatal connectivity. We also develop a moderate-throughput non-contact axotomy assay. Cortical axons in conduits are severed by a media jet; then, brain-derived neurotrophic factor and striatal neurons in distal chambers promote axon regeneration. As additional conduits and chambers are easily added, this opens up the possibility of mimicking complex neuronal networks, and screening drugs for their effects on connectivity.

bioengineering↗

bioRxiv2023

Tracking the Metabolic Fate of Exogenous Arachidonic Acid in Ferroptosis Using Dual-Isotope Labeling Lipidomics

Lipid metabolism is implicated in a variety of diseases, including cancer, cell death, and inflammation, but lipidomics has proven to be challenging due to the vast structural diversity over a narrow range of mass and polarity of lipids. Isotope labeling is often used in metabolomics studies to follow the metabolism of exogenously added labeled compounds because they can be differentiated from endogenous compounds by the mass shift associated with the label. The application of isotope labeling to lipidomics has also been explored as a method to track the metabolism of lipids in various disease states. However, it can be difficult to differentiate a single isotopically labeled lipid from the rest of the lipidome due to the variety of endogenous lipids present over the same mass range. Here we report the development of a dual-isotope deuterium labeling method to track the metabolic fate of exogenous polyunsaturated fatty acids, e.g, arachidonic acid (AA), in the context of ferroptosis using hydrophilic interaction-ion mobility-mass spectrometry (HILIC-IM-MS). Ferroptosis is a type of cell death that is dependent on lipid peroxidation. The use of two isotope labels rather than one enables the identification of labeled species by a signature doublet peak in the resulting mass spectra. A Python-based software, D-Tracer, was developed to efficiently extract metabolites with dual-isotope labels. The labeled species were then identified with Lipydomics based on their retention times, collision cross section, and m/z values. Changes in exogenous AA incorporation in the absence and presence of a ferroptosis inducer were elucidated. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/542640v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@6bbc67org.highwire.dtl.DTLVardef@11e3a84org.highwire.dtl.DTLVardef@193ce6eorg.highwire.dtl.DTLVardef@d5b757_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

In-vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed metabolism in patient-derived xenografts (tumorgrafts) from diverse forms of RCC. Tumorgrafts from VHL-mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engage in oxidative and reductive glutamine metabolism. We used several approaches to suppress glutamine metabolism and test the effect on tumor growth. Genetic silencing of isocitrate dehydrogenase-1 or -2 impaired reductive labeling of TCA cycle intermediates and suppressed tumor growth. Glutaminase inhibition resulted in modest growth suppression and variable effects on glutamine metabolism in vivo. Infusions with [amide-15N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the amidotransferase inhibitor JHU-083 also reduced tumor growth. We conclude that ccRCC tumorgrafts catabolize glutamine via multiple pathways, perhaps explaining why it has been challenging to achieve therapeutic responses in patients by inhibiting glutaminase. TeaserGlutamine fuels the TCA cycle and amidotransferase pathways in clear cell renal cell carcinoma.

cancer biology↗

bioRxiv2022

Assessing evidence accumulation and rule learning in humans with an online game

Evidence accumulation, how the brain integrates sensory information over time, is an essential component of perception and decision making. In humans, evidence accumulation is commonly modeled as a diffusion process in which noise accumulates linearly with the incoming evidence. However, recent studies in rodents have shown that during perceptual decision making, noise scales non-linearly with the strength of accumulated evidence. The question of whether nonlinear noise scaling also holds for humans has been clouded by differences in the methodologies typically used to collect and analyze human and rodent data. For example, whereas humans are typically given explicit instructions in these tasks, rodents are trained using feedback. Therefore, to evaluate how perceptual noise scales with accumulated evidence, we developed an online evidence accumulation game and nonverbal training pipeline for humans inspired by pulse-based evidence accumulation tasks for rodents. Using this game, we collected and analyzed behavioral data from hundreds of participants trained either with an explicit description of the relevant decision rule or merely with experiential feedback. Across all participants, performance was well described by an accumulation process, in which stimuli were integrated equally across time. Participants trained using feedback alone learned the game rules rapidly and used similar strategies to those who received explicit instructions. Decisions in both groups were influenced in similar ways by biases and perceptual noise, suggesting that explicit instructions did not reduce bias or noise in pulse-based accumulation tasks. Finally, by leveraging data across all participants, we show that perceptual noise during evidence accumulation was best described by a non-linear model of noise scaling, consistent with previous animal studies, but inconsistent with diffusion models widely used in human studies. These results challenge the conventional description of humans accumulation process and suggest that online games inspired by evidence accumulation tasks provide a valuable large-scale behavioral assessment platform to examine perceptual decision making and learning in humans. In addition, the feedback-based training pipeline developed for this game may be useful for evaluating perceptual decision making in human populations with difficulty following verbal instructions. HighlightsO_LIDevelopment and validation of an online video game to measure perceptual decision making. C_LIO_LIHumans trained using a feedback-based pipeline exhibit similar strategies and performance compared with those receiving instructions. C_LIO_LIPerceptual noise increases superlinearly with sensory evidence. C_LI

animal behavior and cognition↗

bioRxiv2018

Target specific routing of visual information by the superior colliculus

Using sensory information to trigger different behaviours relies on circuits that pass-through brain regions. However, the rules by which parallel inputs are routed to different downstream targets is poorly understood. The superior colliculus mediates a set of innate behaviours, receiving input from ~30 retinal ganglion cell types and projecting to behaviourally important targets including the pulvinar and parabigeminal nucleus. Combining transsynaptic circuit tracing with in-vivo and ex-vivo electrophysiological recordings we observed a projection specific logic where each collicular output pathway sampled a distinct set of retinal inputs. Neurons projecting to the pulvinar or parabigeminal nucleus uniquely sampled 4 and 7 cell types, respectively. Four others innervated both pathways. The visual response properties of retinal ganglion cells correlated well with those of their disynaptic targets. These findings suggest that projection specific sampling of retinal inputs forms a mechanistic basis for the selective triggering of visually guided behaviours by the superior colliculus.

neuroscience↗