bioRxiv Science⌕ Search

Biology subjects

Zaslaver, A.

Publications and source records attributed to Zaslaver, A..

11 recordsLinked to original sources

Nonlinear sensory integration drives configural olfactory representations

Natural environments are composed of complex stimulus mixtures that can be perceived either as combinations of known components (elemental coding) or acquire entirely new qualities (configural coding). While configural representation is traditionally viewed as a high-order emergent property of cortical processing, the underlying circuit mechanisms remain elusive. Employing C. elegans, we demonstrate that the neural foundations of configural representation can be established already at the sensory periphery. For most mixtures, single neuron responses arise through linear integration of the individual components. However, for a subset of mixtures, a small number of sensory neurons exhibit strong nonlinear integration, including NAND/XOR-like logic-gates computations. These nonlinear integrations collectively generate configural population codes. We present a novel quantitative predictor of configural representation and demonstrate that mixtures classified as configural induce emergent synergistic attraction and may lead to violations of rational choice behavior. Together, our findings identify single-neuron nonlinearities as a mechanistic link between sensory circuit dynamics and complex perceptual and decision-making outcomes.

neuroscience↗

SegBio: A lightweight end-to-end toolkit for Instance Segmentation of biological samples

High-throughput phenotyping of biological samples is essential for large-scale studies but is frequently bottlenecked by the need for accurate instance segmentation in crowded images. While deep learning offers powerful solutions, the high cost of manual annotation and the requirement for coding expertise often limit adoption in routine laboratory workflows. Here we present SegBio, a lightweight, open-source pipeline that enables end-to-end instance segmentation for non-expert users. The protocol features an interactive annotation GUI that extrapolates full masks from minimal centerline markings, significantly reducing manual labeling effort. It further integrates a configurable U-Net training module and a standalone inference application with a human-in-the-loop editing workflow for rapid and intuitive error correction. We employ the pipeline to annotate and train the model on a novel dataset of crowded C. elegans images. Validated on independent datasets, SegBio achieves high segmentation performance (Panoptic quality [~]0.85) and accurately quantifies per-animal morphology and fluorescence. By eliminating external dependencies and streamlining the correction process, SegBio provides a scalable solution for routine phenotyping that is easily generalized to other crowded biological samples, such as cellular organelles, cells, and organisms.

bioinformatics↗

The C. elegans gustatory receptor homolog LITE-1 is a chemoreceptor required for diacetyl avoidance

The nematode C. elegans does not have eyes but can respond to aversive UV and blue light stimulation and even distinguish colours. The gustatory receptor homolog LITE-1 was identified in forward genetic screens for worms that failed to respond to blue light stimulation. When LITE-1 is expressed in body-wall muscles, it causes contraction in response to blue light suggesting that LITE-1 is both necessary and sufficient for blue light response. Here we show that in addition to light avoidance, LITE-1 is also required for worms avoidance of high concentrations of diacetyl, an odorant that is attractive at low concentrations. Like blue light, diacetyl causes muscle contraction in transgenic worms engineered to express LITE-1 in body-wall muscles. These data are consistent with a direct chemoreceptor function for LITE-1 which would make it a multimodal sensor of aversive stimuli.

neuroscience↗

Emergence of clustered synapses during the development of a nervous system

Synaptic organization is central for proper transmission of neural information. Studies in invertebrates and mammalian cortices show that synapses are clustered along neurite extensions, an organization that promotes key functional roles. Here we studied how these synaptic clusters emerge during the development of a nervous system. Leveraging the available C. elegans connectomes that span all larval developmental stages, we show that clustered synapses are formed at the early stages of the neural network development and that their occurrence further increases throughout development. These synaptic clusters significantly constitute small neural circuits that endow the network with important functional roles, such as feedback between mutually synapsing neurons and information transfer in mutually regulated neurons. Moreover, clustered synapses emerge early on during development of the head motor system, where they facilitate the crucial 3D head swings. Finally, the synaptic clusters within these key neural circuits are maintained throughout all developmental stages and are robustly found across different individuals, further accentuating their central functional roles in neural networks.

neuroscience↗

Disposition of the chemosensory neurons in the neurotransmitter-release mutant unc-13

Secretion of neurotransmitters- and neuropeptides-containing vesicles is a regulated process orchestrated by multiple proteins. Of these, mutants, defective in the unc-13 and unc-31 genes, responsible for neurotransmitter and neuropeptide release, respectively, are routinely used to elucidate neural and circuitry functions. While these mutants result in severe functional deficits, their neuroanatomy is assumed to be intact. Here, using C. elegans as the model animal system, we find that the head sensory neurons show aberrant positional layout in neurotransmitter (unc-13), but not in neuropeptide (unc-31), release mutants. This finding suggests that synaptic activity may be important for proper cell migration during neurodevelopment and warrants considering possible anatomical defects when using unc-13 neurotransmitter release mutants.

neuroscience↗

Intricate response dynamics enhances stimulus discrimination in the resource-limited C. elegans chemosensory system

Sensory systems evolved intricate designs to accurately encode perplexing environments. However, this encoding task may become particularly challenging for animals harboring a small number of sensory neurons. Here, we studied how the compact resource-limited chemosensory system of C. elegans uniquely encodes a range of chemical stimuli. We find that each stimulus is encoded using a small and unique subset of neurons, where only a portion of the encoding neurons sense the stimulus directly, and the rest are recruited via inter-neuronal communication. Furthermore, while most neurons show stereotypical response dynamics, some neurons exhibit versatile dynamics that are either stimulus specific or network-activity dependent. Notably, it is the collective dynamics of all responding neurons which provides valuable information that ultimately enhances stimulus identification, particularly when required to discriminate between closely-related stimuli. Together, these findings demonstrate how a compact and resource-limited chemosensory system can efficiently encode and discriminate a diverse range of chemical stimuli.

neuroscience↗

The synaptic organization in the C. elegans neural network suggests significant local compartmentalized computations

Neurons are characterized by elaborate tree-like dendritic structures that support local computations by integrating multiple inputs from upstream presynaptic neurons. It is less clear if simple neurons, consisting of a few or even a single neurite, may perform local computations as well. To address this question, we focused on the compact neural network of C. elegans animals for which the full wiring diagram is available, including the coordinates of individual synapses. We find that the positions of the chemical synapses along the neurites are not randomly distributed, nor can they be explained by anatomical constraints. Instead, synapses tend to form clusters, an organization that supports local compartmentalized computations. In mutually-synapsing neurons, connections of opposite polarity cluster separately, suggesting that positive and negative feedback dynamics may be implemented in discrete compartmentalized regions along neurites. In triple-neuron circuits, the non-random synaptic organization may facilitate local functional roles, such as signal integration and coordinated activation of functionally-related downstream neurons. These clustered synaptic topologies emerge as a guiding principle in the network presumably to facilitate distinct parallel functions along a single neurite, effectively increasing the computational capacity of the neural network.

neuroscience↗

A GPCR negative feedback loop underlies efficient coding of external stimuli

Efficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatio-temporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron in C. elegans worms can cell-autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly-changing continuous gradients. This encoding relies on a simple negative feedback in the GPCR signaling pathway in which TAX-6/Calcineurin plays a key role in mediating the feedback inhibition. Crucially, this negative feedback pathway supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradients first derivative. A simple mathematical model accurately captured the fine neural dynamics of both wt and tax-6 mutant animals, further highlighting how the calcium-dependent activity of TAX-6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a universal solution for efficient cell-autonomous coding of external stimuli.

systems biology↗

Inheritance of associative memories in C. elegans ‎nematodes

The notion that associative memories may be transmitted across generations is intriguing, yet controversial. Here, we trained C. elegans nematodes to associate an odorant with stressful starvation conditions, and surprisingly, this associative memory was evident two generations down of the trained animals. The inherited memory endowed the progeny with a fitness advantage, as memory reactivation induced rapid protective stress responses that allowed the animals to prepare in advance for an impending adversity. Sperm, but not oocytes, transmitted the associative memory, and the inheritance required H3K9 and H3K36 methylations, the small RNA-binding Argonaute NRDE-3, and intact neuropeptide secretion. Remarkably, activation of a single chemosensory neuron sufficed to induce a serotonin-mediated systemic stress response in both the parental trained generation and in its progeny. These findings challenge long-held concepts by establishing that associative memories may indeed be transferred across generations.

neuroscience↗

Principles for coding associative memories in a compact neural network

A major goal in neuroscience is to elucidate the principles by which memories are stored in a neural network. Here, we have systematically studied how the four types of associative memories (short- and long-term memories, each formed using positive and negative associations) are encoded within the compact neural network of C. elegans worms. Interestingly, short-term, but not long-term, memories are evident in the sensory system. Long-term memories are relegated to inner layers of the network, allowing the sensory system to resume innate functionality. Furthermore, a small set of sensory neurons is allocated for coding short-term memories, a design that can increase memory capacity and limit non-innate behavioral responses. Notably, individual sensory neurons may code for the conditioned stimulus or the experience valence. Interneurons integrate these information to modulate animal behavior upon memory reactivation. This comprehensive study reveals basic principles by which memories are encoded within a neural network, and highlights the central roles of sensory neurons in memory formation.

neuroscience↗

Salient Experiences are Represented by Unique Transcriptional Signatures in the Brain

Inducible transcription is essential for consolidation of salient experiences into long-term memory. However, the question of whether inducible transcription relays information representing the identity of the experience being encoded, has not been explored. To this end, we have analyzed transcription across multiple brain regions, induced by a variety of rewarding and aversive experiences. Our results define robust transcriptional signatures uniquely characterizing individual salient experiences. A subset of these induced transcriptional markers suffice for near-perfect decoding of the identity of recent experiences at the level of individual mice. Furthermore, experiences with shared attributes display commonalities in their transcriptional representation, exemplified in the representation of valence, habituation and reinforcement. Taken together, our results demonstrate the existence of a neural transcriptional code that represents the encoding of experiences in the mouse brain. This code is comprised of distinct transcriptional signatures that correlate to the affective attributes of the experiences that are being encoded.

neuroscience↗