Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling

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. Environmental temperature affects neuronal development and functions. However, it is largely unknown whether and how the temperature affects the neurodevelopment, specifically at the level of synaptic specificity. In this study, we found that high cultivation temperature results in the deficits in synaptic specificity. The high temperature induced synaptic defect requires the conserved vesicular glutamate transporter EAT-4 and the inhibitory glutamate gated chloride channels GLC-3 and GLC-4 receptors. These findings uncover a critical role of glutamatergic transmission in regulating synaptic specificity, and provide potential pathological insights into the high temperature related neurological disorders.