Biology subjects

Seyedolmohadesin, M.

Publications and source records attributed to Seyedolmohadesin, M..

10 recordsLinked to original sources

bioRxiv2026

Measuring neuronal input-output operations in vivo with random access projection microscopy

Neurons transform thousands of synaptic inputs into spiking output, and understanding this transformation requires measuring many submicron synapses at millisecond timescales in vivo. Here we present SLAP2, a two-photon random access projection microscope with no per-target access time cost, yielding over 5-fold faster imaging than existing methods, and performant real-time hardware motion correction. Flexible scanning modes enable measurement of hundreds of synapses at ~200 Hz, >800 synapses volumetrically at 50-100 Hz, and compartment-resolved dendritic voltage at 2-10 kHz in behaving mice. Simultaneous dendritic glutamate and somatic calcium imaging in visual cortex pyramidal neurons revealed nonlinear input-output amplification of stimulus onset and preferred stimulus orientation responses. Amplified features are associated with spatially organized inputs and stronger trial-to-trial coupling between synaptic activity and somatic output. These measurements establish SLAP2 as a powerful tool for recording intricate patterns of subcellular fluorescence dynamics in behaving animals.

neuroscience↗

bioRxiv2026

GIAnT: a Glutamate Imaging Analysis Toolbox

Recent advances in fluorescent indicators and optical microscopy now enable in vivo synaptic imaging of glutamate, which transmits the majority of signals between neurons in the brain. Extracting fluorescence signals from these recordings is complicated by the minuscule scale and dense clustering of synapses on dendrites, as well as brain motion in behaving animals. Here we present the Glutamate Imaging Analysis Toolbox (GIAnT), a set of automated tools for glutamate imaging data that corrects sample motion, identifies active synapses with super-resolution precision, and extracts synaptic fluorescence signals. Compared to methods designed for cellular imaging, GIAnT reduces motion artifacts, more accurately identifies active synapses, and improves extracted signal quality by reducing contamination from overlapping synapses. By pairing in vivo glutamate imaging with post hoc expansion microscopy, we find that >70% of the putative synapses extracted using GIAnT matched one-to-one with glutamatergic synapses onto the postsynaptic cell. Our results establish GIAnT as an automated and validated pipeline for processing synaptic glutamate imaging data at scale.

neuroscience↗

bioRxiv2026

Ultrasensitive voltage imaging reveals distinct electrical microdomains in neurons

For the brain to compute, electrical signals must propagate over the membranes of individual neurons, connecting synaptic inputs to synaptic outputs1. Complex neuronal morphologies coupled with the spatial organization of synaptic inputs and outputs enable diverse voltage transformations that underlie cell-type specific computations2,3. However, measuring these transformations in vivo has remained challenging, leaving a crucial gap in our mechanistic understanding of single neuron computation. Here, we develop ASAP7y, a genetically encoded voltage indicator with unprecedented subthreshold sensitivity and expanded excitation compatibility in both mice and flies. We leveraged ASAP7y combined with two-photon random-access microscopy to record sensory stimulus-evoked voltage dynamics with millisecond, subcellular, and subthreshold resolution along the neurites of individual neurons in Drosophila. We found remarkable heterogeneity in voltage propagation across cell-types, delineating a fundamental axis of electrical diversity. Leveraging a nanoscale EM reconstruction of the visual system4, we modeled the electrotonic properties of single neurons spanning 717 cell types, revealing how morphology shapes voltage transformations. Finally, we demonstrate that confined voltage propagation creates substrates for local computation, producing subcellular domains with distinct feature selectivity across multiple cell types. These results provide mechanistic insight into how critical single neuron computations arise and reveal parallel processing in single neurons.

neuroscience↗

bioRxiv2026

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↗

bioRxiv2025

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↗

bioRxiv2024

Neuronal activity regulating the dauer entry decision in Caenorhabditis elegans

The model nematode Caenorhabditis elegans can choose between two alternative developmental trajectories. Larvae can either become reproductive adults or, under conditions of crowding or low food availability, enter a long-term, stress-resistant diapause known as the dauer stage. Previous studies showed that chemical signals from a secreted larval pheromone promote the dauer trajectory, and that their influence can be antagonised by increased availability of microbial food. The decision is known to be under neuronal control, involving both sensory and interneurons. To make an accurate decision, larvae must collect and compare complex patterns of environmental input over several hours of early larval development. The full composition of this circuit and the algorithm for decision-making are unknown. Here, we used cell-specific chemical silencing to systematically perturb several sensory and interneurons to further elucidate circuit composition. Our results suggest a role for gas-sensing neurons in regulating dauer entry. In addition, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA neurons. We found that calcium in ASI increases linearly in response to food, and similarly decreases in response to pheromone, revealing a cellular site of antagonism between these key chemical inputs. Notably, the ASI response persists well beyond removal of the food stimulus, thus encoding a memory of recent food exposure. In contrast, AIA reports instantaneous food availability, and is unaffected by pheromone. We discuss how these findings may inform our understanding of this long-term decision-making process.

neuroscience↗

bioRxiv2024

Sensory integration of food availability and population density during the diapause exit decision involves insulin-like signaling in Caenorhabditis elegans

Decisions made over long time scales, such as life cycle decisions, require coordinated interplay between sensory perception and sustained gene expression. The Caenorhabditis elegans dauer (or diapause) exit developmental decision requires sensory integration of population density and food availability to induce an all-or-nothing organismal-wide response, but the mechanism by which this occurs remains unknown. Here, we demonstrate how the ASJ chemosensory neurons, known to be critical for dauer exit, perform sensory integration at both the levels of gene expression and calcium activity. In response to favorable conditions, dauers rapidly produce and secrete the dauer exit-promoting insulin-like peptide INS-6. Expression of ins-6 in the ASJ neurons integrate population density and food level and can reflect decision commitment since dauers committed to exiting have higher ins-6 expression levels than those of non-committed dauers. Calcium imaging in dauers reveals that the ASJ neurons are activated by food, and this activity is suppressed by pheromone, indicating that sensory integration also occurs at the level of calcium transients. We find that ins-6 expression in the ASJ neurons depends on neuronal activity in the ASJs, cGMP signaling, a CaM-kinase pathway, and the pheromone components ascr#8 and ascr#2. We propose a model in which decision commitment to exit the dauer state involves an autoregulatory feedback loop in the ASJ neurons that promotes high INS-6 production and secretion. These results collectively demonstrate how insulin-like peptide signaling helps animals compute long-term decisions by bridging sensory perception to decision execution. Summary/Significance StatementAnimals must respond appropriately to multiple sensory stimuli to make informed decisions. It remains unclear how the nervous system is able to integrate different sensory cues and propagate that information towards making decisions over longer timescales. We use the nematode Caenorhabditis elegans to investigate how sensory integration occurs during the decision to exit diapause, a stress-resistant developmentally arrested state triggered by multiple sensory inputs including food availability and population density. We show how expression of an insulin-like peptide critical to dauer exit reflects the sensory integration process and decision commitment, and we dissect the regulation of this insulin-like peptides expression. Our study explicitly analyzes the relationship between neuronal activity and neuropeptide expression during a complex decision with diverse sensory inputs.

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bioRxiv2022

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.

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bioRxiv2021

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↗

bioRxiv2021

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↗