Anatomical restructuring of a lateralized neural circuit during associative learning by asymmetric insulin signaling

• Published in: Current biology Vol. 33; no. 18; pp. 3835 - 3850.e6
• Main Authors: Tang, Leo T.H., Lee, Garrett A., Cook, Steven J., Ho, Jacquelin, Potter, Cassandra C., Bülow, Hannes E.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 25.09.2023
• Subjects: associative learning; brain asymmetry; circuit; conditioning; connectome; insulin; learning; neuron; plasticity; synapse; associative learning; circuit; insulin; conditioning; neuron; connectome; plasticity; learning; synapse; brain asymmetry
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2023.07.041

Studies of neuronal connectivity in model organisms, i.e., of their connectomes, have been instrumental in dissecting the structure-function relationship of nervous systems. However, the limited sample size of these studies has impeded analyses into how variation of connectivity across populations may influence circuit architecture and behavior. Moreover, little is known about how experiences induce changes in circuit architecture. Here, we show that an asymmetric salt-sensing circuit in the nematode Caenorhabditis elegans exhibits variation that predicts the animals’ salt preferences and undergoes restructuring during salt associative learning. Naive worms memorize and prefer the salt concentration they experience in the presence of food through a left-biased neural network architecture. However, animals conditioned at elevated salt concentrations change this left-biased network to a right-biased network. This change in circuit architecture occurs through the addition of new synapses in response to asymmetric, paracrine insulin signaling. Therefore, experience-dependent changes in an animal's neural connectome are induced by insulin signaling and are fundamental to learning and behavior. •Adult C. elegans restructure the connectome in response to experience•Associative learning requires lateralized rewiring of a neural circuit•Asymmetric insulin-signaling coordinates anatomical rewiring of neural circuits•Changed network architecture correlates with animal behavior Tang et al. show that asymmetric, paracrine neuronal insulin-signaling anatomically restructures an asymmetric sensory circuit. This restructuring of the neural network occurs in response to the experience of changed environmental conditions and is fundamental for an associative learning paradigm.