Altered reactivity to threatening stimuli in Drosophila models of Parkinson's disease, revealed by a trial-based assay

Kajtor, M.; Billes, V. A.; Kiraly, B.; Stabb, H.; Sviatko, K.; Ujvari, E.; Balazsfi, D.; Seidenbecher, S. E.; Kvitsiani, D.; Vellai, T.; Hangya, B.

doi:10.1101/2023.08.29.555311

bioRxiv · 10.1101/2023.08.29.555311

Altered reactivity to threatening stimuli in Drosophila models of Parkinson's disease, revealed by a trial-based assay

Kajtor, M.·Billes, V. A.·Kiraly, B.·Stabb, H.·Sviatko, K.·Ujvari, E.·Balazsfi, D.·Seidenbecher, S. E.·Kvitsiani, D.·Vellai, T.·Hangya, B.

View original source ↗Export metadata ↓

Abstract

The fruit fly Drosophila melanogaster emerges as an affordable, genetically tractable model of behavior and brain diseases. However, despite the surprising level of evolutionary conservation from flies to humans, significant genetic, circuit-level and behavioral differences hinder the interpretability of fruit fly models for human disease. Therefore, to allow a more direct fly-versus-human comparison, we surveyed the rarely exploited, rich behavioral repertoire of fruit flies with genetic alterations relevant to Parkinsons disease (PD), including overexpression of human mutant Parkin or -synuclein proteins and mutations in dopamine receptors. Flies with different genetic backgrounds displayed variable behaviors, including freezing, slowing and running, in response to predator-mimicking passing shadows used as threatening stimuli in a single-animal trial-based assay. We found that the expression of human mutant Parkin in flies resulted in reduced walking speed and decreased reactivity to passing shadows. Flies with dopamine receptor mutations showed similar alterations, consistent with the motor and cognitive deficits typical in humans with PD. We also found age-dependent trends in behavioral choice during the fly lifespan, while dopamine receptor mutant flies maintained their decreased general reactivity throughout all age groups. Our data demonstrate that single-trial behavioral analysis can reveal subtle behavioral changes in mutant flies that can be used to further our understanding of disease pathomechanisms and help gauge the validity of genetic Drosophila models of neurodegeneration, taking us one step closer to bridging the gap in fly-to-human translation.

Source connections

Published article ↗

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Kajtor, M., Billes, V. A., Kiraly, B., Stabb, H., Sviatko, K., Ujvari, E., Balazsfi, D., Seidenbecher, S. E., Kvitsiani, D., Vellai, T., Hangya, B.. 2023-08-31. Altered reactivity to threatening stimuli in Drosophila models of Parkinson's disease, revealed by a trial-based assay. https://doi.org/10.1101/2023.08.29.555311

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Attention Across Scales: From Individual Variation to Social Hierarchies and Brain Networks in Semi-Free-Ranging Macaques

Attention is a fundamental brain function supporting perception, decision-making, and social behavior, and its dysfunction profoundly impairs daily life. It is both dynamic and stable, varying across observations and individuals, changing across the lifespan, and being shaped by social and environmental experience. Yet capturing this complexity remains a central challenge in neuroscience. Here, we integrated longitudinal behavioral assessments of semi-free-ranging macaques living in naturalistic social groups with resting-state fMRI. We quantified performance across days, ages, and social hierarchies and related it to intrinsic brain organization. Distinct attentional phenotypes emerged, including individuals with reduced attentional control. Performance followed an inverted-U lifespan trajectory, improving from childhood to adulthood before declining. Social status modulated attentional performance. Critically, nonlinear lifespan trajectories and associations with individual attentional differences were most clearly expressed in frontoparietal connectivity. Together, these findings reveal how sustained attention is organized across scales, providing a biological framework for its individual diversity, social modulation, and neural basis.

neuroscience↗

bioRxiv2026

Decoding natural scenes from patterned optogenetic responses in mouse visual cortex

A central challenge in developing visual cortical prostheses is to determine how visual stimuli should be transformed into effective patterns of cortical stimulation. Although advances in stimulation technologies, including optogenetics, provide increasingly precise control over cortical activity, it remains unclear whether artificially evoked activity can reproduce the information content of naturally evoked visual representations. Here we establish a quantitative framework for evaluating visual encoding strategies by decoding cortical responses evoked by natural vision and patterned optogenetic stimulation. We developed a novel dual-modal paradigm in awake mice to bridge the gap between endogenous photostimulation and artificial network driving. By co-expressing the high-performance calcium indicator GCaMP6s and the red-shifted, ultra-sensitive opsin rsChRmine-oScarlet in the primary visual cortex (V1), we successfully translated dynamic natural movie frames into patterned, spatiotemporal optogenetic stimulation. Quantitative comparisons of macro-scale dynamics demonstrated that this patterned optogenetic injection evokes cortical states highly comparable and representationally aligned with those driven by actual visual photostimulation. To systematically evaluate the fidelity of these responses, we developed STAR, a deep learning model featuring spatial and temporal attention mechanisms, and successfully reconstructed the frames of natural movies from V1 signals under both experimental modalities. Collectively, our results demonstrate that complex sensory information can be both naturally encoded and synthetically injected into V1 circuits with high decoding fidelity. This work provides an empirical and computational proof-of-concept for intelligent, closed-loop biomimetic encoders, establishing a robust framework for next-generation cortical visual neuroprostheses and bidirectional brain-machine interfaces.

neuroscience↗

bioRxiv2026

Why Is Spontaneous Blink Timing Informative? An Adaptive Scheduling Perspective

Spontaneous eye blinks have long been linked to cognitive processing, yet how task demands shape blink timing and its relationship to behavioral performance remains unclear. We examined spontaneous blink behavior in 576 adults performing two variants of the Continuous Performance Task (CPT). Blink occurrence and timing were most strongly modulated by the experimental condition in the more demanding CPT-AX task, whereas their association with response time was stronger in the CPT-X task, where more consistent blink timing predicted faster responses. This dissociation suggests that task structure changes not only blink behavior but also the behavioral relevance of blink timing. These findings are consistent with an adaptive scheduling account of spontaneous blinking and provide a conceptual framework for understanding when and why blink timing contains chronometric information about ongoing cognition.

neuroscience↗