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Kadobianskyi, M.

Publications and source records attributed to Kadobianskyi, M..

6 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗