Biology subjects

Atanas, A. A.

Publications and source records attributed to Atanas, A. A..

5 recordsLinked to original sources

bioRxiv2024

Neural Sequences Underlying Directed Turning in C. elegans

Complex behaviors like navigation rely on sequenced motor outputs that combine to generate effective movement. The brain-wide organization of the circuits that integrate sensory signals to select and execute appropriate motor sequences is not well understood. Here, we characterize the architecture of neural circuits that control C. elegans olfactory navigation. We identify error-correcting turns during navigation and use whole-brain calcium imaging and cell-specific perturbations to determine their neural underpinnings. These turns occur as motor sequences accompanied by neural sequences, in which defined neurons activate in a stereotyped order during each turn. Distinct neurons in this sequence respond to sensory cues, anticipate upcoming turn directions, and drive movement, linking key features of this sensorimotor behavior across time. The neuromodulator tyramine coordinates these sequential brain dynamics. Our results illustrate how neuromodulation can act on a defined neural architecture to generate sequential patterns of activity that link sensory cues to motor actions.

neuroscience↗

bioRxiv2024

Deep Neural Networks to Register and Annotate the Cells of the C. elegans Nervous System

Aligning and annotating the heterogeneous cell types that make up complex cellular tissues remains a major challenge in the analysis of biomedical imaging data. Here, we present a series of deep neural networks that allow for automatic non-rigid registration and cell identification, developed in the context of freely moving and deforming invertebrate nervous systems. A semi-supervised learning approach was used to train a C. elegans registration network (BrainAlignNet) that aligns pairs of images of the bending C. elegans head with single pixel-level accuracy. When incorporated into an image analysis pipeline, this network can link neurons over time with 99.6% accuracy. This network could also be readily purposed to align neurons from the jellyfish Clytia hemisphaerica, an organism with a vastly different body plan and set of movements. A separate network (AutoCellLabeler) was trained to annotate >100 neuronal cell types in the C. elegans head based on multi-spectral fluorescence of genetic markers. This network labels >100 different cell types per animal with 98% accuracy, exceeding individual human labeler performance by aggregating knowledge across manually labeled datasets. Finally, we trained a third network (CellDiscoveryNet) to perform unsupervised discovery of >100 cell types in the C. elegans nervous system: by comparing multi-spectral imaging data from many animals, it can automatically identify and annotate cell types without using any human labels. The performance of CellDiscoveryNet matched that of trained human labelers. These tools should be immediately useful for a wide range of biological applications and should be straightforward to generalize to many other contexts requiring alignment and annotation of dense heterogeneous cell types in complex tissues.

neuroscience↗

bioRxiv2024

Pathogen infection induces sickness behaviors by recruiting neuromodulatory systems linked to stress and satiety in C. elegans

When animals are infected by a pathogen, peripheral sensors of infection signal to the brain to coordinate a set of adaptive behavioral changes known as sickness behaviors. While the pathways that signal from the periphery to the brain have been intensively studied in recent years, how central circuits are reconfigured to elicit sickness behaviors is not well understood. Here we find that neuromodulatory systems linked to stress and satiety are recruited upon infection to drive sickness behaviors in C. elegans. Upon chronic infection by the bacterium Pseudomonas aeruginosa PA14, C. elegans decrease their feeding behavior, then display reversible bouts of quiescence, and eventually die. The ALA neuron and its neuropeptides FLP-7, FLP-24, and NLP-8, which control stress-induced sleep in uninfected animals, promote the PA14-induced feeding reduction. However, the ALA neuropeptide FLP-13 instead acts to delay quiescence and death in infected animals. Cell-specific genetic perturbations show that the neurons that release FLP-13 to delay quiescence in infected animals are distinct from ALA. A brain-wide imaging screen reveals that infection-induced quiescence involves ASI and DAF-7/TGF-beta, which control satiety-induced quiescence in uninfected animals. Our results suggest that a common set of neuromodulators are recruited across different physiological states, acting from distinct neural sources and in distinct combinations to drive state-dependent behaviors.

neuroscience↗

bioRxiv2023

Dissecting the Functional Organization of the C. elegans Serotonergic System at Whole-Brain Scale

Serotonin controls many aspects of animal behavior and cognition. But how serotonin acts on its diverse receptor types in neurons across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release from a feeding-responsive neuron in C. elegans alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. A comprehensive genetic analysis identifies three core serotonin receptors that collectively induce slow locomotion upon serotonin release and three others that interact with them to further modulate this behavior. The core receptors have different functional roles: some induce behavioral responses to sudden increases in serotonin release, whereas others induce responses to persistent release. Whole-brain calcium imaging reveals widespread serotonin-associated brain dynamics, impacting different behavioral networks in different ways. We map out all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict serotonin-associated brain-wide activity changes. These results provide a global view of how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.

neuroscience↗

bioRxiv2022

Brain-wide representations of behavior spanning multiple timescales and states in C. elegans

Changes in an animals behavior and internal state are accompanied by widespread changes in activity across its brain. However, how neurons across the brain encode behavior and how this is impacted by state is poorly understood. We recorded brain-wide activity and the diverse motor programs of freely-moving C. elegans and built probabilistic models that explain how each neuron encodes quantitative features of the animals behavior. By determining the identities of the recorded neurons, we created, for the first time, an atlas of how the defined neuron classes in the C. elegans connectome encode behavior. Many neuron classes have conjunctive representations of multiple behaviors. Moreover, while many neurons encode current motor actions, others encode recent actions. Changes in behavioral state are accompanied by widespread changes in how neurons encode behavior, and we identify these flexible nodes in the connectome. Our results provide a global map of how the cell types across an animals brain encode its behavior.

neuroscience↗