Mind of a dauer: Comparative connectomics reveals developmental plasticity

Abstract

A fundamental question in neurodevelopmental biology is how flexibly the nervous system can change during development. To address this question of developmental plasticity, we analyzed the connectome of dauer, an alternative developmental stage of nematodes with physiological and behavioral characteristics remarkably distinct from other developmental stages. We reconstructed the complete chemical connectome of a dauer by manual volumetric reconstruction and automated synapse detection using deep learning. While the basic architecture of the nervous system was preserved, there were also structural changes in neurons, large or small, that were closely associated with changes in the connectivity, some of which in turn evoked dauer-specific behaviors such as nictation. Combining the connectome data and optogenetic experiments were enough to reveal dauer-specific neural connections for the dauer-specific behavior. Graph theoretical analyses showed higher clustering of motor neurons and more feedback connections from motor to sensory neurons in the dauer connectome, suggesting that the dauer connectome allows a quick response to an ever-changing environment. We suggest that the nervous system in the nematode, which can be extended to animals in general, has evolved to obtain the ability to respond to harsh environments by reversibly developing a connectome quantitatively and qualitatively differentiated from other developmental stages.

Distinct neurogenetic mechanisms establish the same chemosensory valence state at different life stages in Caenorhabditis elegans

“…For example, the AIY neurons promote CO 2 attraction in starved adults but not dauers ( Fig. 4a ), consistent with the dauer-specific loss of chemical synapses between BAG and AIY ( Yim et al 2023 ). However, AIY still displays CO 2 -evoked activity in dauers ( Banerjee et al 2023 ), suggesting that this activity is independent of BAG-AIY chemical synapses.…”

“…1a ) ( Banerjee et al 2023 ), which may in part reflect differences in synaptic connectivity of these interneurons with the BAG neurons at the two life stages ( Fig. 1a ) ( White et al 1986 ; Varshney et al 2011 ; Bhattacharya et al 2019 ; Yim et al 2023 ). To understand the contribution of these different interneurons to CO 2 attraction at the two life stages, we used a CO 2 chemotaxis assay ( Supplementary Fig.…”

“… Distinct interneurons establish CO 2 attraction in starved adults vs dauers. a) Synaptic connectivity of the BAG neurons with downstream interneurons and their CO 2 -evoked neuronal activity in adults vs dauers ( White et al 1986 ; Rengarajan et al 2019 ; Banerjee et al 2023 ; Yim et al 2023 ). The lighter shade of the BAG neurons in dauers indicates a reduced CO 2 -evoked calcium response, as previously reported ( Banerjee et al 2023 ).…”

Toolkits for detailed and high-throughput interrogation of synapses in C. elegans

“…The nematode Caenorhabditis elegans was the first organism for which a full nervous system connectome was established ( White et al, 1986 ). Connectomes now exist for both sexes ( Cook et al, 2019 ; Hall and Russell, 1991 ; White et al, 1986 ), the pharynx ( Cook et al, 2020 ; Albertson and Thomson, 1976 ), for different developmental stages ( Brittin et al, 2021 ; Witvliet et al, 2021 ), and for the dauer diapause stage ( Yim et al, 2023 ). However, due to the laboriousness of acquiring and analyzing electron microscopy (EM) images and the resulting small sample sizes, our understanding of many aspects of synaptic connectivity has remained limited.…”

Toolkits for detailed and high-throughput interrogation of synapses inC. elegans

“…The nematode C. elegans was the first organism for which a full nervous system connectome was established (White et al, 1986). Connectomes now exist for both sexes (Cook et al 2019; Hall and Russell, 1991; White et al 1986), the pharynx (Cook et al 2020; Albertson and Thomson, 1976), for different developmental stages (Brittin et al, 2021; Witvliet et al 2021), and for the dauer diapause stage (Yim et al 2023). However, due to the laboriousness of acquiring and analyzing electron microscopy (EM) images and the resulting small sample sizes, our understanding of many aspects of synaptic connectivity has remained limited.…”