Biology subjects

Wyart, C.

Publications and source records attributed to Wyart, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Unraveling phenotypic variation in multiscale behavioral dynamics

Behavioral variability reflects differences in internal and external parameters and provides a substrate for natural selection. However, uncovering its structure is challenging because behavior evolves nonlinearly across multiple timescales. Our goal is to reconstruct phenotypic variation from finite behavioral observations without prescribing the scales at which individuals should be compared. To achieve this, we introduce a multiscale dissimilarity that compares dynamics across all statistically resolvable resolutions by constructing reduced transfer operators at progressively finer scales and weighting their differences by finite-sampling uncertainty. This dissimilarity defines a geometry of dynamical phenotypes, which we reconstruct using diffusion maps. We show that the resulting phenotypic coordinates locally follow the parameter directions to which dynamics are most sensitive. We validate our approach in a stochastic model and apply it to bacterial and larval zebrafish behavior. In bacteria, we identify run speed as a major component of inter-individual variability, associated with the chemotaxis protein CheB. In zebrafish, we find that prior prey experience reshapes behavioral dynamics and phenotypic variability, with paramecia experience concentrating fish in a prey-capture-associated region of phenotypic space. Together, these results provide a framework for identifying internal and environmental variables that structure dynamical phenotypes across scales.

biophysics↗

bioRxiv2026

Whole brain mapping of spinal-projecting neurons in larval zebrafish

To elicit voluntary movements and integrative reflexes underlying behavior, the brain sends command signals to the spinal cord via specialized long-range descending neurons, known as spinal-projecting neurons (SPNs). The vast and widespread distribution of SPNs, combined with their complex long-distance connectivity, poses a significant challenge for mapping their anatomical organization and associating specific populations with distinct functions. Here we took advantage of the transparency and genetic accessibility of larval zebrafish to uncover the fundamental principles of SPN anatomical organization in a Teleost. Using an optical backfilling method relying on photoactivable GFP, we generate a whole-brain map of all neurons sending axons towards the spinal cord. This approach reveals far more SPNs than previously described through conventional strategies, offering an unparalleled opportunity to revisit distinct spinal-projecting nuclei distributed across hindbrain, midbrain, and diencephalic structures. Combining information on cell location, morphology, and projection patterns, we propose tentative homological designations for zebrafish of SPN nuclei based on established descriptions in mammals and other vertebrates.

neuroscience↗

bioRxiv2026

Diverse paths for chemoreception in ciliated neurons contacting the cerebrospinal fluid in the spinal cord

Cerebrospinal fluid-contacting neurons (CSF-cNs) are mechanosensory cells in the spinal cord that detect compression and regulate locomotion, posture, and morphogenesis. Although CSF-cNs respond to changes in pH, neurotransmitters and metabolites, their chemosensory repertoire is not fully understood. Using hybridization chain reaction, we investigated the distribution of expression of chemoreceptors in CSF-cNs and neighboring cells in the spinal cord. We found that CSF-cNs express receptors for glutamate (grm2), somatostatin (sstr2) and low-density lipoprotein (LDL) (ldlrad2), indicating roles in detecting glutamate, somatostatin and LDL in the CSF. High LDL receptor expression in CSF-contacting cells suggests CSF lipid capture. Most receptors were enriched but not exclusive to CSF-cNs and also appeared in ependymal radial glial cells. Our findings indicate multiple chemosensory pathways can sustain long-distance communication between neurons and glia through the cerebrospinal fluid.

neuroscience↗

bioRxiv2026

Noradrenaline prolongs the state of motor arrest via cerebrospinal fluid signaling

Neuromodulators can mediate whole-body physiological changes, however how signaling from relatively small populations of neurons produces widespread and sustained effects remains incompletely understood. Here, we demonstrate that sustained noradrenergic activation induces prolonged motor arrest accompanied by postural collapse, bradycardia, and emetic responses. Motor suppression arises from inhibition of brainstem commands to the spinal cord rather than motoneuron silencing. Noradrenaline induces a glial calcium wave that propagates throughout the central nervous system. This wave most prominently persists at the brainstem-spinal cord boundary and ventricular midline. At this location, ependymal radial glia express Adra1a receptors on cilia contacting cerebrospinal fluid (CSF). Ventricular noradrenaline injections recapitulated the glial wave and motor arrest, while CSF administration of an Adra1 antagonist shortened motor arrest. Altogether, noradrenaline sustains motor arrest by signaling through the CSF via ciliary Adra1a receptors on ependymal radial glia showing that cerebrospinal fluid as a critical transmission route for persistence of behavioral states. HighlightsO_LINoradrenergic surges coordinate a whole-body response with motor arrest, postural disruptions, bradycardia, and emesis-like reflexes C_LIO_LIMotor arrest results from silencing of brainstem motor commands to the spinal cord C_LIO_LINoradrenaline-induced glial calcium waves last longest at the obex/ventricular midline where cilia of CSF-contacting glial cells bear Adra1 receptors C_LIO_LINoradrenergic signaling in the CSF is necessary and sufficient for motor arrest to persist C_LI

neuroscience↗

bioRxiv2026

Body-segment coordination as a new predictor of freezing of gait in people with Parkinson disease

Freezing of gait (FOG) in Parkinsons disease (PD) involves impaired integration of posture and locomotion with altered body-segment coordination. We measured coordination using gait kinematics during walking in 16 PD patients with FOG, preoperatively with and without dopaminergic medication (OFF/ON-DOPA), and postoperatively with and without subthalamic deep brain stimulation (OFF/ON-DBS). Body-segment coordination was modeled from acceleration-based intersegmental correlations across trunk, pelvis, and limbs. We tested whether coordination metrics predict individual postoperative FOG severity using LASSO regression with nested cross-validation, including preoperative demographics, clinical scores, gait and coordination metrics. Preoperatively, DOPA decreased trunk-pelvis-upper-limb coordination but increased crossed upper-lower-limbs coupling; while STN-DBS selectively increased inter-upper-limb coordination, with DOPA- and STN-DBS-induced changes being correlated. Whole-body coordination predicted individual postoperative FOG severity, with the most important couplings being the trunk-pelvis and pelvis-lower-limb. Body-segment coordination captures clinically relevant gait metrics in PD, highlighting coordination as a potential biomarker for patient stratification and treatment response.

neuroscience↗

bioRxiv2025

Whole-body central processing of lateral line inputs encodes flow direction relative to the center-of-mass

From shifting visual scenes to tactile deformations and fluid motion, animals must interpret patterns of sensory flow around their body to construct stable internal models and produce adaptive behavior. Understanding of how such transformations are encoded within the brain remains incomplete. To tackle this question, we leverage the lateral line of larval zebrafish as a tractable sensory system sensitive to fluid motion that is used to steer navigation, feed, and avoid predators. By presenting stimuli of either direction to neuromasts along the body, we used high-resolution calcium imaging to map hindbrain responses. Unexpectedly, our findings challenge the notion that central lateral line processing lacks topographic structure by revealing a simple yet powerful principle centered on a egocentric spatial framework: the direction and location of local flow motions are encoded in reference to the animals center-of-mass. This simple representation enables the brain to register complex flow patterns and provides a robust basis for subsequent behavioral action selection. MON neurons that encode flow toward the center-of-mass broadly project to form bilateral connections onto reticulospinal neurons that coordinate forward locomotion while MON neurons that encode flow away from the center-of-mass displayed a more selective and unilateral projection profile to command neurons for turns. Our discovery represents a shift from purely somatotopic encoding toward an integrative representation of axial position and directionality combined, revealing a novel principle of encoding spatio-directional cues in the hindbrain. This study advances our understanding of how complex mechanosensory inputs select appropriate motor outputs via simple egocentric neural maps in the hindbrain. Significance StatementSpatial and directional cues are essential to select appropriate actions in response to changes in the environment. How information from broadly distributed mechanosensors across the entire body occurs in the brain enables motor selection remains elusive. By directionally stimulating each and virtually all neuromasts distributed along the lateral line of larval zebrafish, our study uncovers that spatial and directional inputs from each flow sensors is encoded in the medial octavolateralis nuclei relative to the animals center-of-mass in order to subsequently recruit reticulospinal neurons driving forward and turn bouts. These results establish a new framework for understanding how broadly distributed inputs get integrated to recruit motor command neurons responsible for producing diverse behaviors.

neuroscience↗

bioRxiv2024

Norepinephrine changes behavioral state via astroglial purinergic signaling

Both neurons and glia communicate via diffusible neuromodulatory substances, but the substrates of computation in such neuromodulatory networks are unclear. During behavioral transitions in the larval zebrafish, the neuromodulator norepinephrine drives fast excitation and delayed inhibition of behavior and circuit activity. We find that the inhibitory arm of this feedforward motif is implemented by astroglial purinergic signaling. Neuromodulator imaging, behavioral pharmacology, and perturbations of neurons and astroglia reveal that norepinephrine triggers astroglial release of adenosine triphosphate, extracellular conversion into adenosine, and behavioral suppression through activation of hindbrain neuronal adenosine receptors. This work, along with a companion piece by Lefton and colleagues demonstrating an analogous pathway mediating the effect of norepinephrine on synaptic connectivity in mice, identifies a computational and behavioral role for an evolutionarily conserved astroglial purinergic signaling axis in norepinephrine-mediated behavioral and brain state transitions.

neuroscience↗

bioRxiv2024

Uncovering multiscale structure in the variability of larval zebrafish navigation

Animals chain movements into long-lived motor strategies, resulting in variability that ultimately reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build models that bridges across time scales that enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish exposed to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising and wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive (dark) stimuli or in search for prey. Our method enables us to encode the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies. By doing so, we uncover a hierarchical structure to the phenotypic variability that corresponds to exploration-exploitation trade-offs. Within a wide range of sensory cues, a major source of variation among fish is driven by prior and immediate exposure to prey that induces exploitation phenotypes. However, a large degree of variability is unexplained by environmental cues, pointing to hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, our approach extracts the timescales of motor strategies deployed during navigation, exposing undiscovered structure among individuals and pointing to internal states tuned by prior experience.

animal behavior and cognition↗

bioRxiv2023

SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation

Reissners fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid (CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CSF-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the body axis, and enables proper alignment of the spine. In mammalian models, RF has been implicated in CSF circulation. However, challenges in manipulating Sspo, an exceptionally large gene of 15,719 nucleotides, with traditional approaches has limited progress. Here, we generated a Sspo knockout mouse model using CRISPR/Cas9-mediated genome-editing. Sspo knockout mice lacked RF-positive material in the SCO and fibrillar condensates in the brain ventricles. Remarkably, Sspo knockout brain ventricle sizes were reduced compared to littermate controls. Minor defects in thoracic spine curvature were detected in Sspo knockouts, which did not alter basic motor behaviors tested. Altogether, our work in mouse demonstrates that SSPO and RF regulate ventricle size during development but only moderately impact spine geometry.

neuroscience↗

bioRxiv2023

The Reissner fiber under tension in vivo shows dynamic interaction with ciliated cells contacting the cerebrospinal fluid

The Reissner fiber (RF) is an acellular thread positioned in the midline of the central canal that aggregates thanks to the beating of numerous cilia from ependymal radial glial cells (ERGs) generating flow in the central canal of the spinal cord. RF together with cerebrospinal fluid (CSF)-contacting neurons (CSF-cNs) forms an axial sensory system detecting curvature. How RF, CSF-cNs and the multitude of motile cilia from ERGs interact in vivo appears critical for maintenance of RF and sensory functions of CSF-cNs to keep a straight body axis but is not well-understood. Using in vivo imaging in larval zebrafish, we show that RF is under tension and resonates dorsoventrally. Focal RF ablations trigger retraction and relaxation of the fiber cut ends, with larger retraction speeds for rostral ablations. We built a mechanical model that estimates RF stress diffusion coefficient at 4 mm2 / s and reveals that tension builds up rostrally along the fiber. After RF ablation, CSF-cN spontaneous activity decreased and ciliary motility changed, suggesting physical interactions between RF and cilia projecting into the central canal. We observed that motile cilia were caudally-tilted and frequently interacted with RF. We propose that the numerous ependymal motile monocilia contribute to RF heterogenous tension via weak interactions. Our work demonstrates that under tension, the Reissner fiber dynamically interacts with motile cilia generating CSF flow and spinal sensory neurons.

biophysics↗

bioRxiv2022

Lateral line hair cells integrate mechanical and chemical cues to orient navigation

The lateral line is a superficial sensory system responding to environmental hydrodynamic changes to orient locomotion of aquatic vertebrate species. Whether this system also detects chemical cues is unknown. We find that zebrafish lateral line hair cells express numerous chemoreceptors, including ionotropic receptors for serotonin. We show that the serotonin enriched in skin neuroepithelial cells is released upon injury and that environmental serotonin activates lateral line hair cells. We show that larval zebrafish exposed to serotonin in their environment rely on the lateral line to swim fast and away. These results uncover the sensory versatility of lateral line hair cells and how these properties modulate navigation in response to environmental stimuli.

neuroscience↗

bioRxiv2022

Granger causality analysis for calcium transients in neuronal networks: challenges and improvements

One challenge in neuroscience is to understand how information flows between neurons in vivo to trigger specific behaviors. Granger causality (GC) has been proposed as a simple and effective measure for identifying dynamical interactions. At single-cell resolution however, GC analysis is rarely used compared to directionless correlation analysis. Here, we study the applicability of GC analysis for calcium imaging data in diverse contexts. We first show that despite underlying linearity assumptions, GC analysis successfully retrieves non-linear interactions in a synthetic network simulating intracellular calcium fluctuations of spiking neurons. We highlight the potential pitfalls of applying GC analysis on real in vivo calcium signals, and offer solutions regarding the choice of GC analysis parameters. We took advantage of calcium imaging datasets from motoneurons in embryonic zebrafish to show how the improved GC can retrieve true underlying information flow. Applied to the network of brainstem neurons of larval zebrafish, our pipeline reveals strong driver neurons in the locus of the mesencephalic locomotor region (MLR), driving target neurons matching expectations from anatomical and physiological studies. Altogether, this practical toolbox can be applied on in vivo population calcium signals to increase the selectivity of GC to infer flow of information across neurons.

neuroscience↗

bioRxiv2022

Functional coupling of the mesencephalic locomotor region and V2a reticulospinal neurons driving forward locomotion

Locomotion in vertebrates relies on high brain centers converging onto the mesencephalic locomotor region (MLR). How the MLR recruits brainstem reticulospinal neurons (RSNs) to initiate locomotion is incompletely understood due to the challenge of recording these cells in vivo. To tackle this question, we leveraged the transparency and genetic accessibility of larval zebrafish. In this model organism, we uncovered the locus of the MLR as a small region dorsal to the locus coeruleus containing glutamatergic and cholinergic neurons. MLR stimulations reliably elicited forward bouts of controlled duration and speed. We find that the MLR elicits forward locomotion by recruiting V2a RSNs in the pontine and retropontine regions, and gradually in the medulla. Remarkably, recruited V2a RSNs in the medulla act as maintain cells encoding speed of forward locomotion. Altogether, our study reveals that the MLR recruits genetically-identified reticulospinal neurons in the medulla to control the kinematics of exploration.

neuroscience↗

bioRxiv2021

Spinal sensory neurons project onto hindbrain to stabilize posture and enhance locomotor speed

In the spinal cord, cerebrospinal fluid-contacting neurons (CSF-cNs) are GABAergic interoceptive sensory neurons that detect spinal curvature via a functional coupling with the Reissner fiber. This mechanosensory system has recently been found involved in spine morphogenesis and postural control but the underlying mechanisms are not fully understood. In zebrafish, CSF-cNs project an ascending and ipsilateral axon reaching two to six segments away. Rostralmost CSF-cNs send their axons ipsilaterally into the hindbrain, a brain region containing motor nuclei and reticulospinal neurons (RSNs), which send descending motor commands to spinal circuits. Until now, the synaptic connectivity of CSF-cNs has only been investigated in the spinal cord where they synapse onto motor neurons and premotor excitatory interneurons. The identity of CSF-cN targets in the hindbrain and the behavioral relevance of these sensory projections from spinal cord to hindbrain are unknown. Here, we provide anatomical and molecular evidence that rostralmost CSF-cNs synapse onto the axons of large RSNs including the Mauthner cells and early born chx10+ neurons. Functional anatomy and optogenetic-assisted mapping reveal that rostral CSF-cNs also synapse onto the soma and dendrites of cranial motor neurons innervating hypobranchial muscles. During acousto-vestibular evoked escape responses, ablation of rostralmost CSF-cNs results in a weaker escape response with a decreased C-bend amplitude, lower speed and a deficient postural control. Our study demonstrates that spinal sensory feedback enhances speed and stabilizes posture, and reveals a novel spinal gating mechanism acting on the output of descending commands sent from the hindbrain to the spinal cord. eTOCCerebrospinal fluid-contacting neurons are mechanosensory cells that detect spinal curvature. Wu et al. show here that rostralmost CSF-cNs synapse in the hindbrain onto cranial motor neurons and the descending axons of reticulospinal neurons, and enhance speed and power as well as postural control during active locomotion. HighlightsO_LICerebrospinal fluid-contacting neurons (CSF-cNs) in rostral spinal cord form inhibitory synapses onto cranial motor neurons C_LIO_LIRostral CSF-cNs synapse onto descending axons of reticulospinal neurons C_LIO_LICSF-cN sensory feedback in the rostral spinal cord enhance speed and power of locomotion C_LIO_LIRostral CSF-cNs projecting to the hindbrain contribute to postural control C_LI

neuroscience↗

bioRxiv2021

Evolutionary divergence of locomotion in two related vertebrate species

Locomotion exists in diverse forms in nature and is adapted to the environmental constraints of each species1. However, little is known about how closely related species with similar neuronal circuitry can evolve different navigational strategies to explore their environments. We established a powerful approach in comparative neuroethology to investigate evolution of neuronal circuits in vertebrates by comparing divergent swimming pattern of two closely related larval fish species, Danionella translucida (DT) and Danio rerio or zebrafish (ZF)2,3. During swimming, we demonstrate that DT utilizes lower half tail-beat frequency and amplitude to generate a slower and continuous swimming pattern when compared to the burst-and-glide swimming pattern in ZF. We found a high degree of conservation in the brain anatomy between the two species. However, we revealed that the activity of a higher motor region, referred here as the Mesencephalic Locomotion Maintenance Neurons (MLMN) correlates with the duration of swim events and differs strikingly between DT and ZF. Using holographic stimulation, we show that the activation of the MLMN is sufficient to increase the frequency and duration of swim events in ZF. Moreover, we propose two characteristics, availability of dissolved oxygen and timing of swim bladder inflation, which drive the observed differences in the swim pattern. Our findings uncover the neuronal circuit substrate underlying the evolutionary divergence of navigational strategies and how they are adapted to their respective environmental constraints.

neuroscience↗

bioRxiv2020

A lexical approach for identifying behavioral action sequences

Animals display characteristic behavioral patterns when performing a task, such as the spiraling of a soaring bird or the surge-and-cast of a male moth searching for a female. Identifying such recurring sequences occurring rarely in noisy behavioral data is key to understanding the behavioral response to a distributed stimulus in unrestrained animals. Existing models seek to describe the dynamics of behavior or segment individual locomotor episodes rather than to identify the rare and transient sequences of locomotor episodes that make up the behavioral response. To fill this gap, we develop a lexical, hierarchical model of behavior. We designed an unsupervised algorithm called "BASS" to efficiently identify and segment recurring behavioral action sequences transiently occurring in long behavioral recordings. When applied to navigating larval zebrafish, BASS extracts a dictionary of remarkably long, non-Markovian sequences consisting of repeats and mixtures of slow forward and turn bouts. Applied to a novel chemotaxis assay, BASS uncovers chemotactic strategies deployed by zebrafish to avoid aversive cues consisting of sequences of fast large-angle turns and burst swims. In a simulated dataset of soaring gliders climbing thermals, BASS finds the spiraling patterns characteristic of soaring behavior. In both cases, BASS succeeds in identifying rare action sequences in the behavior deployed by freely moving animals. BASS can be easily incorporated into the pipelines of existing behavioral analyses across diverse species, and even more broadly used as a generic algorithm for pattern recognition in low-dimensional sequential data.

animal behavior and cognition↗

bioRxiv2020

Adrenergic activation modulates the signal from the Reissner fiber to cerebrospinal fluid-contacting neurons during development

The cerebrospinal fluid (CSF) contains an extracellular thread that is conserved in vertebrates and referred to as the Reissner fiber. Genetic ablation in the zebrafish revealed that the Reissner fiber controls body axis morphogenesis in the embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not fully understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required for the expression of urp2, a neuropeptide expressed in CSF-cNs. Using in vivo calcium imaging, we show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation directly in the CSF can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results suggest that the Reissner fiber acts on CSF-cNs to establish body axis morphogensis by controlling the availability of a chemical signal in the CSF.

developmental biology↗

bioRxiv2020

A calibrated optogenetic toolbox of stable zebrafish opsin lines

Optogenetic actuators with diverse spectral tuning, ion selectivity and kinetics are constantly being engineered providing powerful tools for controlling neural activity with subcellular resolution and millisecond precision. Achieving reliable and interpretable in vivo optogenetic manipulations requires reproducible actuator expression and calibration of photocurrents in target neurons. Here, we developed nine transgenic zebrafish lines for stable opsin expression and calibrated their efficacy in vivo. We first used high-throughput behavioural assays to compare opsin ability to elicit or silence neural activity. Next, we performed in vivo whole-cell electrophysiological recordings to quantify the amplitude and kinetics of photocurrents and test opsin ability to precisely control spiking. We observed substantial variation in efficacy, associated with differences in both opsin expression level and photocurrent characteristics, and identified conditions for optimal use of the most efficient opsins. Overall, our calibrated optogenetic toolkit will facilitate the design of controlled optogenetic circuit manipulations.

neuroscience↗