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Research Article: New Research, Integrative Systems

Neuronal activity regulating the dauer entry decision in Caenorhabditis elegans

Sharan J. Prakash, Maedeh Seyedolmohadesin, Mark G. Zhang, Sarah M. Cohen, Shahla Gharib, Vivek Venkatachalam and Paul W. Sternberg
eNeuro 26 December 2025, ENEURO.0447-24.2025; https://doi.org/10.1523/ENEURO.0447-24.2025
Sharan J. Prakash
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Maedeh Seyedolmohadesin
2Physics Department, Northeastern University, Boston, MA, USA
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Mark G. Zhang
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Sarah M. Cohen
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Shahla Gharib
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Vivek Venkatachalam
2Physics Department, Northeastern University, Boston, MA, USA
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Paul W. Sternberg
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Abstract

The life cycle of the model nematode Caenorhabditis elegans involves a choice between two alternative developmental trajectories. Hermaphroditic 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. Chemical signals from a secreted larval pheromone promote the dauer trajectory in a concentration-dependent manner, and their influence can be antagonised by increased availability of a microbial food source. The decision is known to be under neuronal control, involving both sensory and interneurons. However, little is known about the dynamics of the underlying circuit, and the circuit mechanisms by which short-term fluctuations in the ratio of food and pheromone experienced by individual larvae are remembered and averaged over several hours. To investigate this, we quantitatively characterized the neuronal responses to food and pheromone inputs by measuring calcium traces from ASI and AIA neurons, each of which has previously been implicated in regulation of dauer entry. We found that calcium in ASI increases linearly in response to food, and similarly decreases in response to pheromone. 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.

Significance Statement The neural circuit underlying the decision to enter the dauer diapause in Caenorhabditis elegans is poorly understood. In particular, it is unclear how fluctuating inputs with opposite effect on the decision are averaged and remembered over several hours to allow accurate decision-making. In this study, we show that a single sensory neuron responds oppositely to chemical cues with opposite effects on the decision, and retains a memory of recent input in a persistent calcium transient. These findings demonstrate how microfluidics and live imaging, combined with neuronal silencing and behaviour assays, can be leveraged to understand the dynamics of the neural circuit regulating the decision.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Neuronal activity regulating the dauer entry decision in Caenorhabditis elegans
Sharan J. Prakash, Maedeh Seyedolmohadesin, Mark G. Zhang, Sarah M. Cohen, Shahla Gharib, Vivek Venkatachalam, Paul W. Sternberg
eNeuro 26 December 2025, ENEURO.0447-24.2025; DOI: 10.1523/ENEURO.0447-24.2025

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Neuronal activity regulating the dauer entry decision in Caenorhabditis elegans
Sharan J. Prakash, Maedeh Seyedolmohadesin, Mark G. Zhang, Sarah M. Cohen, Shahla Gharib, Vivek Venkatachalam, Paul W. Sternberg
eNeuro 26 December 2025, ENEURO.0447-24.2025; DOI: 10.1523/ENEURO.0447-24.2025
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