Biology subjects

Judkewitz, B.

Publications and source records attributed to Judkewitz, B..

13 recordsLinked to original sources

bioRxiv2026

Multimodal reference brain atlas of adult Danionella cerebrum

Mechanistic accounts of brain function require a common coordinate system in which structural, molecular and functional data can be integrated and compared across individuals. The teleost genus Danionella is unique among vertebrates in retaining lifelong transparency, allowing non-invasive, cellular-resolution functional imaging across the entire adult brain. A reference atlas in this model would therefore provide a strong foundation for causal and comparative circuit studies. Here we present an integrated anatomical, molecular and functional reference brain for adult Danionella cerebrum as a standardised atlas resource. Using a transgenic nuclear fluorescence marker, whole-mount tissue clearing and high-resolution two-photon microscopy, we generated an average reference brain from 21 adult fish to create a common coordinate system. Whole-mount in situ hybridisation for 29 neuronal markers, complemented by tract annotation from structural imaging and tracer injections, enabled us to segment 203 neuroanatomical regions. We found pronounced sex differences in telencephalic, cerebellar and hindbrain nuclei, revealing sexually dimorphic organisation across multiple brain regions. All data and segmentations are made openly accessible, providing a community resource for studies of circuit function, molecular makeup and sexual dimorphism in an optically accessible adult vertebrate brain.

neuroscience↗

bioRxiv2026

Brain-wide hierarchical and sexually dimorphic tuning for social vocalizations

Vocal repertoires consist of a limited number of call types, even though their sounds can vary continuously in form. Where in the brain receivers partition this variation into discrete types is contested: different accounts place the emergence of categories in the cortex/pallium or already in the midbrain. Because recordings have been limited to isolated regions, it remains unknown whether this partitioning is confined to a single region at all, occurs in parallel across many, or is built up along the pathway. Here we present the first whole-brain, cellular-resolution analysis of how conspecific vocalizations are categorized in a vertebrate, using the glassfish Danionella cerebrum. We find that categorization is neither pallial nor localized. It begins at the first central auditory nuclei, much earlier than previously thought, where a continuous morph between social and non-social sounds evokes an abrupt switch in population activity. The midbrain then sharpens these representations, and the thalamus filters for species-typical pulse rates while splitting call duration into two discrete populations. Only downstream of this shared code do the sexes diverge in forebrain social nuclei. Call type partitioning is thus distributed and hierarchically assembled, rather than read out at any one stage.

neuroscience↗

bioRxiv2026

Whole-body single-cell atlas of an adult vertebrate in homeostasis and regeneration

A complete cell-type transcriptome atlas of a vertebrate could promote understanding of animal cell-type composition, organization, and evolution. The miniaturized, transparent, and regenerative teleost Danionella cerebrum brings whole-vertebrate single-cell profiling experiments within reach. We performed region-stratified single-cell RNA sequencing across the adult Danionella body and mapped cell types and gene expression at single-cell resolution using spatial transcriptomics. We delineated spatially-distinct neural cell types based on their regional gene expression signatures. The body-wide atlas elucidated cell types harboring adult positional information, uncovered paedomorphic features, and revealed conserved body-region and appendage-specification programs in adult connective tissue. Comparative analyses revealed conserved neural cell types, and regeneration datasets uncovered expression dynamics during telencephalon regeneration. This whole-vertebrate transcriptome atlas yields a comprehensive resource for myriad questions in biology and neuroscience.

systems biology↗

bioRxiv2025

An algorithm underlying directional hearing in fish

Humans and other land vertebrates localize sound by comparing the signals in each ear. Even though these differences are virtually absent underwater, fish are still able to sense the direction of sound. In 1975, Arie Schuijf proposed that this ability could arise from a comparison of the particle motion phase and the pressure phase of sound, a prediction which was recently confirmed experimentally for near-field sounds. In natural environments, however, sounds arrive from variable distances, altering the motion-pressure phase relationship. Thus, directional hearing and distance hearing are potentially at conflict. There is currently neither a model nor experimental data for how fish deal with this complexity. Here, we systematically introduce phase differences to the particle motion and pressure components of sound pulses to quantify the directional tuning of startle responses in Danionella cerebrum. We find that the fishs directed startle behavior is both frequency and phase dependent, and introduce a new model that quantitatively predicts the sensorimotor transformation across all observed stimuli. This framework likely extends to other otophysan fishes with evolutionarily conserved hearing apparatus, representing [~]15% of all vertebrate species. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/693757v3_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@1cff8b5org.highwire.dtl.DTLVardef@d174a1org.highwire.dtl.DTLVardef@1400e0aorg.highwire.dtl.DTLVardef@59cfe3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits

All cells in an animal collectively ensure, moment-to-moment, the survival of the whole organism in the face of environmental stressors1,2. Physiology seeks to elucidate the intricate network of interactions that sustain life, which often span multiple organs, cell types, and timescales, but a major challenge lies in the inability to simultaneously record time-varying cellular activity throughout the entire body. We developed WHOLISTIC (WHole Organism Live Imaging System for recording Tissue and IntraCellular activity), a method to image second-timescale, time-varying intracellular dynamics across cell-types of the vertebrate body. By advancing and integrating volumetric fluorescence microscopy, machine learning, and pancellular transgenic expression of calcium sensors in transparent young Danio rerio (zebrafish) and with proof of concept in adult Danionella, the method enables real-time recording of cellular dynamics across the organism. Calcium is a universal intracellular messenger, with a large array of cellular processes depending on changes in calcium concentration across varying time-scales, making it an ideal proxy of cellular activity3. Using this platform to screen the dynamics of most cells in the body, we discovered unexpected responses of specific cell types to stimuli, such as chondrocyte reactions to cold, meningeal responses to ketamine, and state-dependent activity, such as oscillatory ependymal-cell activity during periods of extended motor quiescence. At the organ scale, the method uncovered pulsating traveling waves along the kidney nephron. At the multi-organ scale, we uncovered muscle synergies and independencies, as well as muscle-organ interactions. Integration with optogenetics allowed us to all-optically determine the causal direction of brain-body interactions. At the whole-organism scale, the method captured the rapid brainstem-controlled redistribution of blood flow across the body. Finally, we advanced Whole-Body Expansion Microscopy4 to provide ground-truth molecular and ultrastructural anatomical context, explaining the spatiotemporal structure of activity captured by WHOLISTIC. Together, these innovations establish a new paradigm for systems biology, bridging cellular and organismal physiology, with broad implications for both fundamental research and drug discovery.

neuroscience↗

bioRxiv2024

High-speed three-dimensional random access scanning with SPARCLS

High-speed volumetric imaging is crucial for observing fast and distributed processes such as neuronal activity. Multiphoton microscopy helps to mitigate scattering effects inside tissue, but the standard raster scanning approach limits achievable volume rates. Random-access scanning can lead to a considerable speed-up by sampling only pre-selected locations, but existing techniques based on acousto-optic deflectors are still limited to a point rate of up to [~]50 kHz. This limits the number of parallel targets at the high acquisition rates necessary, for example, in voltage imaging or imaging of fast synaptic events. Here we introduce SPARCLS, a method for 3D random-access scanning at up to 340 kHz point rate using a single 1D phase modulator. We show the potential of this method by imaging synaptic events with fluorescent glutamate sensors in mammalian organotypic slices as well as in zebrafish larvae.

neuroscience↗

bioRxiv2024

Development of sound production in Danionella cerebrum

Acoustic signaling, integral to intraspecific communication and reproductive behavior, undergoes notable changes during an animals ontogenetic development. The onset and progression of this maturation in fish remains poorly understood. Here, we investigate the ontogeny of acoustic communication in the micro glassfish Danionella cerebrum (DC), one of the smallest known vertebrates and an emerging model organism in neuroscience. Adult DC males produce audible clicks that appear in sequences with a repetition rate of 60 or 120 Hz, caused by consecutive unilateral or alternating bilateral compressions, respectively. To investigate the maturation of this ability, we performed long-term sound recordings and morphological studies of the DC sound production apparatus throughout its ontogenetic development. We found that DC start producing clicks during the second month of their lives and continually increase their abundance and structured repetition over the course of the following one to two months. The sound production machinery, including specialized bone and cartilage structures, start to form in male DC after approximately four weeks and prior to full maturation of the reproductive organs. While the DC clicks increase in amplitude with age and body size, click repetition rates of 60 and 120 Hz are stable throughout development. This suggests a fully developed central pattern generator in juvenile males, yet a continued maturation of the drumming apparatus capable of creating louder sounds.

animal behavior and cognition↗

bioRxiv2023

Fast and light efficient remote focusing for volumetric voltage imaging

Voltage imaging holds great potential for biomedical research by enabling noninvasive recording of the electrical activity of excitable cells such as neurons or cardiomyocytes. Camera-based detection can record from hundreds of cells in parallel, but imaging entire volumes is limited by the need to focus through the sample at high speeds. Remote focusing techniques can remedy this drawback, but have so far been either too slow or light inefficient. Here, we introduce FLIPR, a new approach for remote focusing that doubles the light efficiency and enables high-speed volumetric voltage imaging at 500 volumes/s. We show the potential of our approach by combining it with lightsheet imaging in the zebrafish spinal cord to record from >100 spontaneously active neurons in parallel.

neuroscience↗

bioRxiv2023

Binge Feeding Promotes Appetite via Modulating Olfactory Flavor Representation

Binge eating commonly leads to overeating, but the exact mechanism is unclear. While it is known that experiencing flavor contributes to satiety, the interactions between flavor, feeding rate, and food intake remain unknown. Here, we demonstrate a novel feeding rate-dependent feedback loop between olfactory flavor representation in the anterior olfactory (piriform) cortex (aPC) and food intake. Using miniscopes for in vivo calcium imaging in freely foraging mice, we identified specific excitatory neuronal responses to food and water during slow feeding. Switching to binge feeding transformed these specific responses into unspecific global suppression of neuronal activity. Food consumption was predicted by the degree of suppression of neuronal activity in the aPC during binge feeding. Also, food deprivation enhanced neuronal activity suppression. We confirmed the hypothesis that aPC suppression promotes food intake with closed-loop optogenetics experiments. Together, we show that olfactory sensory representation in the aPC reciprocally interacts with consummatory behavior to enhance food intake.

neuroscience↗

bioRxiv2022

Brain-wide imaging of an adult vertebrate with image transfer oblique plane microscopy

Optical imaging is a powerful tool to visualise and measure neuronal activity. However, due to the size and opacity of vertebrate brains it has until now been impossible to simultaneously image neuronal circuits at cellular resolution across the entire adult brain. This is true even for the smallest known vertebrate brain in the teleost Danionella, which is still too large for existing volumetric imaging approaches. Here we introduce image transfer oblique plane microscopy, which uses a new optical refocusing solution via a custom fibre-optical faceplate, enabling a large field-of-view of up to 4 mm3 at a volume rate of 1 Hz. We demonstrate the power of this method with the first brain-wide recording of neuronal activity in an adult vertebrate.

neuroscience↗

bioRxiv2021

Deep tissue scattering compensation with three-photon F-SHARP

Optical imaging techniques are widely used in biological research, but their penetration depth is limited by tissue scattering. Wavefront shaping techniques are able to overcome this problem in principle, but are often slow and their performance depends on the sample. This greatly reduces their practicability for biological applications. Here we present a scattering compensation technique based on three-photon (3P) excitation, which converges faster than comparable two-photon (2P) techniques and works reliably even on densely labeled samples, where 2P approaches fail. To demonstrate its usability and advantages for biomedical imaging we apply it to the imaging of dendritic spines on GFP-labeled layer 5 neurons in an anesthetized mouse.

bioengineering↗

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↗

bioRxiv2019

Hybrid genome assembly and annotation of Danionella translucida, a transparent fish with the smallest known vertebrate brain

Studying the activity of distributed neuronal circuits at a cellular resolution in vertebrates is very challenging due to the size and optical turbidity of their brains. We recently presented Danionella translucida, a close relative of zebrafish, as a model organism suited for studying large-scale neural network interactions in adult individuals. Danionella remains transparent throughout its life, has the smallest known vertebrate brain and possesses a rich repertoire of complex behaviours. Here we sequenced, assembled and annotated the Danionella translucida genome employing a hybrid Illumina/Nanopore read library as well as RNA-seq of embryonic, larval and adult mRNA. We achieved high assembly continuity using low-coverage long-read data and annotated a large fraction of the transcriptome. This dataset will pave the way for molecular research and targeted genetic manipulation of the smallest known vertebrate brain.

genomics↗