Environmental factors such as temperature affect neuronal activity and development. However, it remains unknown whether and how they affect synaptic subcellular specificity. Here, using the nematode Caenorhabditis elegans AIY interneurons as a model, we found that high cultivation temperature robustly induces defects in synaptic subcellular specificity through glutamatergic neurotransmission. Furthermore, we determined that the functional glutamate is mainly released by the ASH sensory neurons and sensed by two conserved inhibitory glutamate-gated chloride channels GLC-3 and GLC-4 in AIY. Our work not only presents a novel neurotransmission-dependent mechanism underlying the synaptic subcellular specificity, but also provides a potential mechanistic insight into high-temperature-induced neurological defects.
Synaptic connections are essential to build a functional brain. How synapses are formed during development is a fundamental question in neuroscience. Recent studies provided evidence that the gut plays an important role in neuronal development through processing signals derived from gut microbes or nutrients. Defects in gut–brain communication can lead to various neurological disorders. Although the roles of the gut in communicating signals from its internal environment to the brain are well known, it remains unclear whether the gut plays a genetically encoded role in neuronal development. Using C. elegans as a model, we uncover that a Wnt‐endocrine signaling pathway in the gut regulates synaptic development in the brain. A canonical Wnt signaling pathway promotes synapse formation through regulating the expression of the neuropeptides encoding gene nlp‐40 in the gut, which functions through the neuronally expressed GPCR/AEX‐2 receptor during development. Wnt‐NLP‐40‐AEX‐2 signaling likely acts to modulate neuronal activity. Our study reveals a genetic role of the gut in synaptic development and identifies a novel contribution of the gut–brain axis.
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