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Torkashvand, M.

Publications and source records attributed to Torkashvand, M..

5 recordsLinked to original sources

The C. elegans nervous system reads the internal state of the hydrogen peroxide-detoxification machinery to trigger escape from this common reactive chemical

Hydrogen peroxide (H2O2) is the most common reactive chemical threat faced by organisms. Here, we map the neural circuit that drives chemotactic escape from environmental H2O2 in the nematode C. elegans. Twenty-four neuron classes with sensory endings at the mouth and nose of the animal detect H2O2. Their response dynamics encode stimulus intensity and exposure history, and their partial redundancy makes avoidance resilient to the loss of individual inputs. Sensing begins when H2O2 oxidizes the peroxidatic and resolving cysteines of the cytosolic peroxiredoxin PRDX-2, which relays this oxidative signal to cysteines on the LITE-1 and GUR-3 ion channels, triggering calcium influx in sensory neurons that drive escape. Most of these neurons release glutamate to drive H2O2-dependent excitation of AIA interneurons, whereas others signal through non-glutamatergic routes, providing multiple routes for signal transmission. Thus, the C. elegans nervous system acts as a hydrogen peroxide sentinel that monitors H2O2-induced changes in the intracellular H2O2-detoxification machinery and relays them to interneurons driving organism-wide escape. This raises the possibility that circuit defects in aging and neurodegenerative disease arise from altered peroxiredoxin-mediated H2O2 signaling rather than primarily from direct macromolecular damage.

neuroscience↗

Whole-brain chemosensory responses of both C. elegans sexes

Sexually-dimorphic neural circuits play a critical role in shaping sex-specific animal behaviors. Maps of the structural dimorphisms in these circuits have been explored by analyzing "synaptic connectomes", electron micrograph reconstructions of synaptic connectivity. Nevertheless, recent studies in the model organism C. elegans have shown little to no correlation between the synaptic connectome and dynamic neural activity. Therefore, the extent of sexual dimorphism in functional neural activity remains unknown. To determine the extent of functional sexual-dimorphisms in C. elegans we compared activity, neuron-by-neuron, across all neurons in the heads of both sexes. To sample a broad view of responses to different sensory modalities, we tested a diverse panel of ethologically-relevant olfactory, gustatory, and chemical stimuli, representing both attractive and aversive cues. We found that nearly every sensory neuron responded dimorphically to at least one cue and monomorphically to other cues, indicating that sexually-dimorphic circuits are pervasive and stimulus dependent. This dimorphic and monomorphic activity was present to a lesser extent in downstream interneurons and even less so in motoneurons, implicating sensory neurons as the primary source and location of sexually-dimorphic activity. Comparing the functional activity we measured to the published synaptic connectomes of both sexes revealed that sexual dimorphism in functional connectivity was distinct from and complementary to sexual dimorphism in synaptic connectivity. Our results provide a first-of-its-kind comparison of whole-brain dynamics between sexes at the level of single neurons, serving as an extensive resource for further investigations of functional sex differences.

neuroscience↗

Versatile Multiple Object Tracking in Sparse 2D/3D Videos Via Diffeomorphic Image Registration

Tracking body parts in behaving animals, extracting fluorescence signals from cells embedded in deforming tissue, and analyzing cell migration patterns during development all require tracking objects with partially correlated motion. As dataset sizes increase, manual tracking of objects becomes prohibitively inefficient and slow, necessitating automated and semi-automated computational tools. Unfortunately, existing methods for multiple object tracking (MOT) are either developed for specific datasets and hence do not generalize well to other datasets, or require large amounts of training data that are not readily available. This is further exacerbated when tracking fluorescent sources in moving and deforming tissues, where the lack of unique features and sparsely populated images create a challenging environment, especially for modern deep learning techniques. By leveraging technology recently developed for spatial transformer networks, we propose ZephIR, an image registration framework for semi-supervised MOT in 2D and 3D videos. ZephIR can generalize to a wide range of biological systems by incorporating adjustable parameters that encode spatial (sparsity, texture, rigidity) and temporal priors of a given data class. We demonstrate the accuracy and versatility of our approach in a variety of applications, including tracking the body parts of a behaving mouse and neurons in the brain of a freely moving C. elegans. We provide an open-source package along with a web-based graphical user interface that allows users to provide small numbers of annotations to interactively improve tracking results.

neuroscience↗

Interneuron Control of C. elegans Developmental Decision-making

Animals integrate external stimuli to shape their physiological responses throughout development. In adverse environments, Caenorhabditis elegans larvae can enter a stress-resistant diapause state with arrested metabolism and reproductive physiology. Amphid sensory neurons feed into both rapid chemotactic and short-term foraging mode decisions, mediated by amphid and premotor interneurons, as well as the long-term diapause decision. We identify amphid interneurons that integrate pheromone cues and propagate this information via a neuropeptidergic pathways to influence larval developmental fate, bypassing the pre-motor system. AIA interneuron-derived FLP-2 neuropeptide signaling promotes reproductive growth and AIA activity is suppressed by pheromone. FLP-2 acts antagonistically to the insulin-like INS-1. FLP-2s growth promoting effects are inhibited by upstream metabotropic glutamatergic signaling and mediated by the broadly-expressed neuropeptide receptor NPR-30. Conversely, the AIB interneurons and their neuropeptide receptor NPR-9/GALR2 promote diapause entry. These neuropeptidergic outputs allow reuse of parts of a sensory system for a decision with a distinct timescale.

neuroscience↗

Modulation of sensory perception by hydrogen peroxide enables Caenorhabditis elegans to find a niche that provides both food and protection from hydrogen peroxide

Hydrogen peroxide (H2O2) is the most common chemical threat that organisms face. Here, we show that H2O2 alters the bacterial food preference of Caenorhabditis elegans, enabling the nematodes to find a safe environment with food. H2O2 induces the nematodes to leave food patches of laboratory and microbiome bacteria when those bacterial communities have insufficient H2O2-degrading capacity. The nematodes behavior is directed by H2O2-sensing neurons that promote escape from H2O2 and by bacteria-sensing neurons that promote attraction to bacteria. However, the input for H2O2-sensing neurons is removed by bacterial H2O2-degrading enzymes and the bacteria-sensing neurons perception of bacteria is prevented by H2O2. The resulting cross-attenuation provides a general mechanism that ensures the nematodes behavior is faithful to the lethal threat of hydrogen peroxide, increasing the nematodes chances of finding a niche that provides both food and protection from hydrogen peroxide.

neuroscience↗