Biology subjects

Bahl, A.

Publications and source records attributed to Bahl, A..

At least 19 recordsLinked to original sources

bioRxiv2026

An atlas of functional ensembles in the zebrafish hindbrain links structural and molecular features to behavior

The vertebrate hindbrain sustains functions essential for survival and behavioral control, yet how it operates as a whole remains poorly understood. Here we map its functional organization in larval zebrafish, whose transparency permits imaging of the entire hindbrain. We first curate established functional populations from the literature into an atlas annotated with putative mammalian counterparts. We then complement this library with ensembles of co-active neurons extracted without prior labels from whole-hindbrain light-field recordings in behaving larvae. We identify 70 ensembles that recur across individuals and recover most of them in independent light-sheet datasets. Ensembles also align with spatial gene-expression patterns and share their bilateral symmetry. Behavioral characterization identifies known eye- and tail-movement-related populations and reveals new associations with fin and mouth movements. Combining co-activity, molecular signatures, and neuronal projections suggests a candidate recurrent inter-regional circuit. Our atlas thus provides a common spatial reference for linking functional, molecular, and anatomical data to guide circuit discovery.

neuroscience↗

bioRxiv2026

Opposing influences of sensory and response history in larval zebrafish

Variability is a prominent feature of animal behavior across species. Despite highly controlled experimental conditions, the same individual often responds differently to repeated identical stimulation. Part of this variability can be explained by the sequence of previous sensory stimuli and decision-making events - the trial history. Most studies about trial history are limited to animals that have a cortex, such as rodents or primates, observed as they perform learned cognitive tasks. It is currently unknown whether trial history can shape the behavior of animals lacking cortical structures during untrained, naturalistic behaviors. Here, we address this question in larval zebrafish, performing the optomotor response, an innate sensorimotor behavior in which animals turn in the direction of whole-field visual motion. We observed that a substantial proportion of variability can be explained by recent stimulation and decision-making events, with influences lasting for tens of minutes. Intriguingly, sensory and response histories bias the current response in opposite directions - repulsive and attractive, respectively - analogous to what has been previously reported in humans and rodents. An integrator model operating across multiple timescales explains a considerable fraction of response variability based on trial history alone. Our findings demonstrate that history dependency in animal behavior is not an exclusive feature of higher-order cortical computation after learning, but that it reflects a fundamental and evolutionarily shared property of vertebrate sensorimotor systems. SIGNIFICANCE STATEMENTBehavioral variability is often attributed to noise in sensory and neural processing. We show instead that much of this variability can arise predictably from an animals recent sensory and response history. In freely swimming larval zebrafish performing an innate visual behavior, previous stimuli and responses exert opposing, long-lasting influences: sensory history biases behavior away from the past, whereas response history promotes repetition. Such trial-to-trial effects are increasingly recognized in cognitive neuroscience but, to our knowledge, have not previously been demonstrated in a nonmammalian vertebrate. Their presence in zebrafish, a model system offering brain-wide neural access and powerful molecular tools, creates new opportunities to identify potentially conserved circuit mechanisms underlying persistent sensorimotor computations. HIGHLIGHTSO_LIVisual motion and response histories have opposing influences on behavior C_LIO_LIStimulus history negatively biases response direction over tens of seconds C_LIO_LIAnimals tend to repeat responses across trials, a positive bias that slowly increases over minutes C_LIO_LIA deterministic model applied to experimental sessions explains considerable fractions of response variability C_LI

animal behavior and cognition↗

bioRxiv2026

Non-stationary Markovian dynamics shape swim bias fluctuations in zebrafish larvae

Animals are capable of internally modulating behavior as a function of internal state, environmental sensory conditions, and context. Classical models often assume that sensorimotor decisions are driven primarily by external stimuli, with individual biases treated as either constant or evolving monotonically over time. Here, we show that 5-day-old zebrafish larvae display slowly changing directional swim biases even in stable, homogeneous environments, with fluctuations unfolding over many hours. Computational modeling suggests that these biases arise from a non-stationary Markovian process, with two largely independent internal input streams modulating the tendency to repeat swim directions across consecutive swim bouts. These slow fluctuations are present across sensory conditions, including different light intensities and global motion cues, although the switching statistics are modulated by these conditions. Our findings reveal an intrinsic, context-sensitive source of behavioral variability and provide a framework for further study of computational principles that generate spontaneous and adaptive behavior.

animal behavior and cognition↗

bioRxiv2026

Multiscale regulation of experience-dependent plasticity by a Pannexin1 homolog in a developing vertebrate brain

Experience-dependent plasticity enables the developing brain to adapt to repeated sensory input while maintaining stability. However, how such plasticity is coordinated across behavior, transcription, and network dynamics remains unclear. Here, using larval zebrafish, we identify the pannexin channel homolog, Panx1a as a regulator of multiscale adaptations during visual habituation. Panx1a loss selectively impairs long-term habituation without affecting baseline sensorimotor responses. This behavioral deficit is accompanied by disrupted activity-dependent transcription across distributed brain regions and altered excitation-inhibition balance. At the network level, Panx1a deficiency attenuates experience-dependent modulation of gamma activity, cross-frequency coupling, and inter-regional coherence. We further show that sharp wave-ripple-like events are present in vivo at an early developmental stage and exhibit selective refinement of their sharp-wave component following experience, while ripple features remain largely unchanged. This refinement is reduced in panx1a mutants, indicating a role for Panx1a in shaping network dynamics rather than event generation. Together, these findings identify Panx1a as a mediator linking extracellular signaling to coordinated behavioral, molecular, and circuit-level plasticity during early brain development.

neuroscience↗

bioRxiv2026

Developmental and genetic modulation of evidence integration dynamics in zebrafish sensorimotor decision-making

Animals integrate information over time and maintain persistent internal representations of cues to guide decision-making. How the underlying behavioral algorithms of individual animals depend on factors such as experience, developmental stage, or genotype remains poorly understood. Drift-diffusion models provide a powerful theoretical framework to describe and predict performance metrics across a wide range of species. The stochastic nature of these models and the typical limited throughput of most experimental designs challenge the automatic inference of latent variables. Here, we combine high-throughput behavioral assays in larval zebrafish with drift-diffusion modeling, revealing that larvae progressively develop more persistent, self-reinforcing integration dynamics during early development. This effect is reduced in fish carrying mutations in genes linked to human epilepsy and schizophrenia. Our results show that behavior-based drift-diffusion modeling can offer a scalable, automated approach to generate experimentally testable hypotheses about the algorithmic implementation of sensorimotor integration in health and disease. LINK TO VIDEOShttps://cloud.uni-konstanz.de/index.php/s/qx9DSFciAey3aD7 TEASEREvidence-integration dynamics in zebrafish mature during development and are selectively altered by disease-associated mutations.

neuroscience↗

bioRxiv2025

An RNA ligase shapes transcriptional profiles, neural function, and behaviour in the developing larval zebrafish

RNA ligases are essential for the repair, splicing, and editing of RNA across various biological systems. Recently, a new enzyme that catalyses 5-3 RNA ligation - RNA ligase 1 (Rlig1) - was identified in vitro. However, the in vivo biological functions of Rlig1 have remained elusive. Here, we reveal the role of Rlig1 during vertebrate development using embryonic and larval zebrafish as a model system. We found that rlig1 mRNA is maternally deposited and present ubiquitously during early embryogenesis, whereas at larval stages it localises to the brain and eyes. Interestingly, CRISPR/Cas9-generated rlig1 knockout zebrafish exhibited no overt morphological abnormalities, but showed reduced behavioural responsiveness to visual stimuli along with massively perturbed transcriptomes and widespread dysregulation of core metabolic and translational pathways. Brain-wide calcium imaging in rlig1 knockout larvae revealed decreased neuronal activity in key regions for visual processing, consistent with the observed behavioural defects. Together, our findings identify a role for Rlig1 in maintaining the integrity and function of the nervous system and uncover a new link between neuronal RNA processing, development, and sensory-motor computation.

developmental biology↗

bioRxiv2025

Parallel and convergent pathways for multifeature visual processing in larval zebrafish sensorimotor decision-making

Animals continuously extract and evaluate diverse sensory information from the environment to guide behavior. Yet, how neural circuits integrate multiple, potentially conflicting, inputs during decision-making remains poorly understood. Here, we use larval zebrafish to address this question, leveraging their robust optomotor response to coherent random dot motion and phototaxis towards light. We demonstrate that animals employ an additive behavioral algorithm of three visual features: motion coherence, luminance level, and changes in luminance. Using brain-wide two-photon imaging, we identify the loci of these computations, with the anterior hindbrain emerging as a multifeature sensory integration hub. Through single-cell neurotransmitter and morphological analyses of functionally identified neurons, we characterize potential connections within and across computational nodes. These experiments reveal three parallel and converging pathways, matching our behavioral results. Our study provides a mechanistic brain-wide account of how a vertebrate brain integrates multiple features to drive sensorimotor decisions, bridging the algorithmic bases of behavior and its neural implementation.

neuroscience↗

bioRxiv2025

Fishexplorer: A multimodal cellular atlas platform for neuronal circuit dissection in larval zebrafish

Understanding how neural circuits give rise to behavior requires comprehensive knowledge of neuronal morphology, connectivity, and function. Atlas platforms play a critical role in enabling the visualization, exploration, and dissemination of such information. Here, we present FishExplorer, an interactive and expandable community platform designed to integrate and analyze multimodal brain data from larval zebrafish. FishExplorer supports datasets acquired through light microscopy (LM), electron microscopy (EM), and X-ray imaging, all co-registered within a unified spatial coordinate system which enables seamless comparison of neuronal morphologies and synaptic connections. To further assist circuit analysis, FishExplorer includes a suite of tools for querying and visualizing connectivity at the whole-brain scale. By integrating data from recent large-scale EM reconstructions (presented in companion studies), FishExplorer enables researchers to validate circuit models, explore wiring principles, and generate new hypotheses. As a continuously evolving resource, FishExplorer is designed to facilitate collaborative discovery and serve the growing needs of the teleost neuroscience community.

neuroscience↗

bioRxiv2025

Behavioral algorithms of ontogenetic switching in larval and juvenile zebrafish phototaxis

Animals undergo major behavioral adjustments during ontogeny, but how the underlying cognitive algorithms change during this process remains elusive. Here, we describe that zebrafish shift from light-seeking to dark-seeking, as they grow from larval to juvenile stage, within the first few weeks of their life. We apply a combination of complementary phototaxis assays in virtual reality and modeling to dissect the computational basis of this transition. We identify three parallel pathways, one analyzing ambient whole-field luminance levels, one spatially comparing light levels across the eyes, and one computing eye-specific temporal derivatives. Larvae mostly use the latter two spatio-temporal computations for navigation, while juveniles largely employ the first one. We build a library of agent-based models to predict animal behavior across stimulation conditions and in more complex environments. Model-based extraction of latent cognitive variables points towards potential neural correlates of the observed behavioral inversion and illustrates a novel way to explore the processes of vertebrate ontogeny. We suggest that zebrafish phototaxis is regulated via parallel processing streams, which could be a universal implementation to change strategies depending on developmental stage, context, or internal state, making behavior flexible and goal-oriented. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/659371v3_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@40848forg.highwire.dtl.DTLVardef@1bed6c6org.highwire.dtl.DTLVardef@68a10org.highwire.dtl.DTLVardef@1525f06_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIWe provide a framework to describe how behavioral strategies evolve during ontogeny. C_LIO_LIZebrafish switch their phototactic behavior within the first weeks of their life. C_LIO_LIBrightness navigation strategies can be described with a three-pathway model. C_LIO_LILarvae use spatial cues, while juveniles use ambient whole-field luminance for phototaxis. C_LI

animal behavior and cognition↗

bioRxiv2025

A connectomic resource for neural cataloguing and circuit dissection of the larval zebrafish brain

We present a correlated light and electron microscopy (CLEM) dataset from a 7-day-old larval zebrafish, integrating confocal imaging of genetically labeled excitatory (vglut2a) and inhibitory (gad1b) neurons with nanometer-resolution serial section EM. The dataset spans the brain and anterior spinal cord, capturing >180,000 segmented soma, >40,000 molecularly annotated neurons, and 30 million synapses, most of which were classified as excitatory, inhibitory, or modulatory. To characterize the directional flow of activity across the brain, we leverage the synaptic and cell body annotations to compute region-wise input and output drive indices at single cell resolution. We illustrate the datasets utility by dissecting and validating circuits in three distinct systems: water flow direction encoding in the lateral line, recurrent excitation and contralateral inhibition in a hindbrain motion integrator, and functionally relevant targeted long-range projections from a tegmental excitatory nucleus, demonstrating that this resource enables rigorous hypothesis testing as well as exploratory-driven circuit analysis. The dataset is integrated into an open-access platform optimized to facilitate community reconstruction and discovery efforts throughout the larval zebrafish brain.

neuroscience↗

bioRxiv2025

Lrrns define a visual circuit underlying brightness and contrast perception

Brightness and contrast are fundamental features of vision, crucial for object detection, environmental navigation, and feeding. Here, we identify a brightness-and contrast-processing circuit in the zebrafish visual system and uncover the role of Leucine-rich repeat neuronal (Lrrn) cell adhesion molecules (CAMs) in regulating its assembly. Deep-projecting retinal ganglion cells (RGCs) serve as the first synaptic relay to the brain requiring Lrrn2 and Lrrn3a for precise axonal targeting and connectivity within the optic tectum. Genetic targeting of these CAMs leads to circuit disorganization and impairments in contrast sensitivity, leading to deficits in visually guided behaviors. Additionally, ultrastructural circuit reconstruction and functional imaging analysis revealed their critical role in luminance processing. These studies define a fundamental visual processing pathway and establish Lrrn CAMs as essential molecular drivers of its assembly.

neuroscience↗

bioRxiv2025

Early visual experience elicits cellular and functional plasticity in the retina and alters behaviour

Our interaction with the surrounding environment shapes how our brain processes sensory information and drives adaptive behaviour. This plasticity allows the brain to rewire in response to specific sensory experiences. For instance, early manipulation of visual inputs profoundly impacts brain plasticity, which is crucial for functions like size perception, object recognition, and visuospatial processing. While neuronal plasticity has been detected in visual target structures such as the colliculus, thalamus, and cortex, it remains unclear if the retina, the primary sensory organ, undergoes significant plasticity. Here, we show that the zebrafish retina demonstrates pronounced plastic transformations in response to alterations of the visual environment during development, which ultimately modifies the detection of oriented visual stimuli. We demonstrate that orientation-selective amacrine cells undergo profound morphological changes in animals exposed to distinct visual environments during development. We further find that the functional orientation-selective output from the retina is altered in a manner consistent with the visual environment in which the animals are raised and that these changes are persistent. Finally, animals tested in a virtual reality system show that early exposure to different visual environments changes their innate preference for specifically oriented patterns. Our findings unveil a unique developmental form of sensory organ plasticity with continuing structural and functional consequences.

neuroscience↗

bioRxiv2025

Evaluation of Probiotic Bacteria for the Reduction of Urea, p-Cresol, and Indole Levels

IntroductionEnd-stage kidney disease (ESKD) is associated with the accumulation of uremic toxins such as urea, p-cresol, and indole, which significantly contribute to systemic complications such as inflammation, oxidative stress, and gut dysbiosis. Probiotics have demonstrated potential in modulating gut microbiota and reducing these toxins. We evaluated the in vitro efficacy of multiple probiotic strains of Lactobacillus, Bifidobacterium, Sterptococcus, Bacillus and others in degrading urea, p-cresol, and indole. MethodsThe probiotic strains were initially trained on toxin media prior to their evaluation of their toxin breakdown efficiency. Additionally microbiological methods using selective Christiansons broth/agar and Stuarts broth/agar were applied to assess urea breakdown. Liquid Chromatography-Mass Spectrometry (LC-MS) was utilized to quantify p-cresol and indole degradation. ResultsThe results indicated that all probiotic strains exhibited significant activity in reducing urea, p-cresol, and indole concentrations in the culture media. In urea breakdown we observed an oscillation urea/ammonia ratio at 24 hr intervals, although a complete elimination of the ammonium byproduct was not feasible. Among all tested probiotics, Lactobacillus species showed the highest efficiency in urea breakdown. Furthermore, the toxin removing efficacy of the probiotics was evaluated in a simulated gut environment using the TNO invitro gut model. ConclusionCumulatively, the findings suggest that probiotics could offer a promising strategy for the reduction of uremic toxins and their associated complications in ESKD patients.

microbiology↗

bioRxiv2025

Correlative light and electron microscopy reveals the fine circuit structure underlying evidence accumulation in larval zebrafish

AbstractEvidence accumulation is a fundamental neural computation essential for adaptive behavior, yet its synaptic implementation remains unclear. Addressing this challenge critically depends on linking neural dynamics to circuit structure within the same brain. Here, we combine functional calcium imaging with large-scale ultrastructural electron microscopy (EM) to uncover the wiring logic of visual evidence accumulation in larval zebrafish. In a functionally imaged EM dataset of the anterior hindbrain, we identify conserved morphological cell types whose activity patterns define distinct computational roles. Bilateral inhibition, disinhibition, and recurrent connectivity emerge as key circuit motifs shaping these dynamics. To generalize our findings across animals, we develop a photoconversion-based pipeline to label and reconstruct functionally characterized neurons, enabling us to train a classifier that predicts functional identity from morphology alone. Applying this classifier to a second, whole-brain EM dataset lacking functional data reveals matching connectivity patterns, significantly augmenting its applicability for detailed circuit dissections. Based on these results, we develop and constrain a biophysically realistic neural network model that captures observed dynamics and yields predictions we tested and confirmed experimentally. Our work illustrates how hypothesis-driven connectomics can uncover the synaptic basis of sensory-motor computations and establishes a novel framework for cross-animal circuit dissection in the vertebrate brain.

neuroscience↗

bioRxiv2024

Sleep Disruption Improves Performance in Simple Olfactory and Visual Decision-Making Tasks

Sleep disruption drastically impacts cognitive functions including decision-making and attention across many different species. In this study, we leveraged the small size and conserved vertebrate brain structure of larval zebrafish to investigate how sleep disruption modulates visual-and olfactory-decision-making. Strikingly, sleep disruption improved performance in both paradigms. Specifically, sleep disruption lengthens reaction times and increases correct decisions in a visual motion discrimination task, an effect that we attribute to longer integration periods in disrupted animals. Using a drift diffusion model, we predict specific circuit changes underlying these effects. Additionally, we demonstrate that sleep disruption heightens odor sensitivity in an olfactory decision-making task, likely mediated by cortisol. Our findings lay essential groundwork for investigating the brain circuit changes that arise from sleep disruption across species.

neuroscience↗

bioRxiv2024

Pannexin-2 deficient zebrafish develop ocular and visual motor behaviour defects

Pannexin-2 (Panx2) is a unique ion channel localized to ER-mitochondria contact sites. These dynamic and specialized microdomains are abundant in neurons and glia and essential for cellular signaling and metabolism. While synaptic interactions are well-studied, the role of intracellular contacts, such as those of ER-mitochondrial junctions, in neuronal function and neurodegeneration remains largely unexplored. To investigate the roles of Panx2 in neuronal communication, we meticulously examined its expression pattern in the zebrafish brain and used TALEN technology to generate homozygous Panx2 knockout (Panx2{Delta}11) zebrafish. Our results demonstrate that panx2 mRNA is present in several brain regions, notably in visual centers such as the optic tectum and the thalamus. In 6 days post fertilization TL (Panx2+/+) larvae, Panx2 expression was observed in the inner and outer plexiform layers of the retina and the arborization fields of the optic tract. Transcriptome profiling of Panx2{Delta}11 larvae by RNA-seq analysis revealed down-regulation of vision-related genes, specifically those involved in visual and sensory perception and lens development. Behavioral tests showed that loss of Panx2 leads to an altered ability to interpret visual information, such as changes in ambient illuminations, and respond with the characteristic motor action. Panx2{Delta}11 larvae exhibited reduced locomotor activity during light and increased activity during dark phases. Additionally, the knockout larvae displayed significantly impaired optomotor response (OMR). Lastly, when we tested the retinal structure of adult zebrafish eyes using optical coherence tomography (OCT), Panx2{Delta}11 fish revealed a longer mean axial length and a negative shift in retinal refractive error (RRE) values; both indicative of myopia. Our findings highlight a distinct, novel function of Panx2 in retinal development, visual perception, and ocular health, beyond its recognized roles in neurodevelopment and tumor-suppressing properties in cancer cells.

neuroscience↗

bioRxiv2022

Reflective multi-immersion microscope objectives inspired by the Schmidt telescope

Rapid advances in tissue clearing protocols have begun to outpace the capabilities of existing microscope objectives: High-resolution imaging inside cm-sized cleared samples is often not possible as it requires multi-immersion objectives with high numerical aperture (NA > 0.7), long working distance (WD > 10 mm) and a large field-of-view (FOV > 1 mm). Here, we introduce a novel mirror-based optical design, the "Schmidt objective", which meets all these criteria despite containing only two optical elements. It consists of a spherical mirror in contact with the immersion medium and an aspherical correction plate. We showcase a multi-photon variant of a Schmidt objective that reaches NA 1.08 at an refractive index of 1.56 and demonstrate its versatility by imaging fixed samples in a wide range of immersion media ranging from air and water to BABB, DBE, and ECI. In addition, we demonstrate in vivo imaging by recording neuronal activity in larval zebrafish.

neuroscience↗

bioRxiv2022

Systematic analysis of the molecular and biophysical properties of key DNA damage response factors

Repair of DNA double strand breaks (DSBs) is integral to preserving genomic integrity. Therefore, defining the mechanisms underlying DSB repair will enhance our understanding of how defects in these pathways contribute to human disease and could lead to the discovery of new approaches for therapeutic intervention. Here, we established a panel of HaloTagged DNA damage response factors in U2OS cells which enables concentration-dependent protein labeling. Genomic insertion of the HaloTag at the endogenous loci of the repair factors preserves expression levels and proteins retain proper subcellular localization, foci-forming ability, and functionally support DSB repair. We systematically analyzed total cellular protein abundance, measured recruitment kinetics to DSBs, and defined the diffusion dynamics and chromatin binding by live-cell single-molecule imaging. Our work demonstrates that the Shieldin complex, a critical factor in end joining, does not exist in a preassembled state and Shieldin components are recruited to DSBs with different kinetics. Additionally, live-cell single-molecule imaging revealed the constitutive interaction between MDC1 and chromatin mediated by the PST repeat domain of MDC1. Altogether, our studies demonstrate the utility of single-molecule imaging to provide mechanistic insights into DNA repair, which will serve as a powerful resource for characterizing the biophysical properties of DNA repair factors in living cells.

cell biology↗