Abstract
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.
Highlights
Normal brain functions require precise synaptic connectivity among billions of neuronal and non-neuronal cells
We showed that the AIY ectopic synaptic formation in cima-1 loss-of-function mutants requires the inhibitory glutamate signaling, which is mediated by the ASH expressed vesicular glutamate transporter EAT-4 and the AIY expressed pLGIC family glutamate gated chloride channels GLC-3 and GLC-4
We found that eat-4 completely rescued and restored the ectopic synapses in cima-1(wy84);eat-4 double mutants when expressed in the nervous system with rab-3 promoter [63], or in the glutamatergic neurons with eat-4a promoter (S3A Fig, [64]), but not in the ventral cephalic sheath cells (VCSC) glia, epidermis, muscle, intestine or AIY interneurons with hlh-17, dpy-7, myo-3, ges-1 and ttx-3 promoters respectively [65,66,67,68,69] (Fig 2A and 2B)
Summary
Normal brain functions require precise synaptic connectivity among billions of neuronal and non-neuronal cells. Temperature regulates synaptic specificity through inhibitory glutamatergic signaling. Shanghai Municipal Science and Technology Major Project (No 2018SHZDZX01) and ZJLab to ZS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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