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Inberg, S.

Publications and source records attributed to Inberg, S..

3 recordsLinked to original sources

Behavioral age-detection in individuals reconstructs minute-scale developmental transcriptomics

Capturing rapid changes in gene-expression across development time is crucial for uncovering the molecular pathways that organize dynamic developmental processes. Here, we introduce BehaveSeq, a method that enables time reconstruction of minute-resolution developmental patterns of gene-expression by integrating longitudinal behavioral monitoring for precise age detection with genome-wide transcriptomic profiling in single individuals. By densely sampling individuals every [~]3 minutes during hours of C. elegans development, we uncovered thousands of genes exhibiting rapid and temporally structured expression trajectories. These genes were organized into distinct dynamical patterns associated with specific developmental functions. Moreover, time-reconstruction of transcriptional trajectories in serotonin-deficient individuals revealed time-specific neuromodulatory effects on developmental expression programs. Interestingly, using the same single-animal datasets, we were able to train a neural network model that accurately predicts the developmental age of each individual based on its individual-specific molecular signature. Overall, our method provides a new framework for revealing dynamic gene regulation with high temporal precision across developmental timescales.

developmental biology↗

Neurodegeneration impairs the consolidation of developmentally synchronized behavioral patterns

Animals generate predictable patterns of behavior that are robustly synchronized with the developmental clock. However, the dynamics of the long-term establishment of synchronized behaviors across the entire developmental trajectory, and the neuronal circuits that control this developmental synchronization, remain underexplored. Here, we show that in C. elegans individuals, developmental synchronization of behavior continuously consolidates throughout development time, and that this consolidation is controlled by multiple neuronal pathways. In particular, we found that the degeneration of a specific mechanosensory circuit early in development strongly impairs the developmental synchronization of behavior. Furthermore, early neuronal activity patterns in downstream motor neurons are altered following the mechanosensory circuit degeneration. Interestingly, we show that either pharmacological or genetic neuroprotection of the mechanosensory circuit from degeneration restores normal modes of developmentally synchronized behaviors. These results imply the control of time-locked behaviors across the developmental trajectory by a localized sensory circuit within the nervous system.

neuroscience↗

Sensory experience controls dendritic structure and behavior by distinct pathways involving degenerins

Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the Caenorhabditis elegans arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity- dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli. Significance StatementLittle is known about how neuronal activity and sensory experience influence the structure and function of dendritic trees. Furthermore, how dendritic structures affect neuronal functions remains to a large extent a mystery despite their fundamental functions in neuronal sensory and synaptic activities in health and diseases. Here we show that complex dendritic trees of the nociceptive and proprioceptive PVD neuron in C. elegans display a dynamic nature where they undergo pronounced dendritic modifications during adulthood. These modifications are determined by the received sensory signals generated by conspecific worms on the plate or by inert glass beads. We revealed functions for degenerins/Epithelial sodium channels in this phenomenon, using genetic and optogenetic approaches. We found that the degenerin MEC-10 acts cell autonomously to translate environmental mechanical signals into structural and functional modifications in the PVD.

neuroscience↗