PDF(Pubmed)
Abstract：
Physiological dysfunction confers negative valence to coincidental sensory cues to induce the formation of aversive associative memory. How peripheral tissue stress engages neuromodulatory mechanisms to form aversive memory is poorly understood. Here, we show that in the nematode C. elegans, mitochondrial disruption induces aversive memory through peroxisomal β-oxidation genes in non-neural tissues, including pmp-4/very-long-chain fatty acid transporter, dhs-28/3-hydroxylacyl-CoA dehydrogenase, and daf-22/3-ketoacyl-CoA thiolase. Upregulation of peroxisomal β-oxidation genes under mitochondrial stress requires the nuclear hormone receptor NHR-49. Importantly, the memory-promoting function of peroxisomal β-oxidation is independent of its canonical role in pheromone production. Peripheral signals derived from the peroxisomes target NSM, a critical neuron for memory formation under stress, to upregulate serotonin synthesis and remodel evoked responses to sensory cues. Our genetic, transcriptomic, and metabolomic approaches establish peroxisomal lipid signaling as a crucial mechanism that connects peripheral mitochondrial stress to central serotonin neuromodulation in aversive memory formation.
摘要：
生理功能失调赋予偶然的感觉线索以负价，以诱导形成厌恶性联想记忆。外周组织应力如何参与神经调节机制以形成厌恶性记忆尚不清楚。这里,我们发现在线虫C.elegans中，线粒体破坏通过非神经组织中的过氧化物酶体β-氧化基因诱导厌恶记忆，包括pmp-4/超长链脂肪酸转运蛋白，dhs-28/3-羟基酰基辅酶A脱氢酶，和daf-22/3-酮酰基-CoA硫解酶。线粒体应激下过氧化物酶体β-氧化基因的上调需要核激素受体NHR-49。重要的是,过氧化物酶体β-氧化的促进记忆功能与其在信息素产生中的典型作用无关。来自过氧化物酶体靶向NSM的外周信号，在压力下形成记忆的关键神经元，上调5-羟色胺合成并重塑对感觉线索的诱发反应。我们的基因，转录组，和代谢组学方法将过氧化物酶体脂质信号传导作为在厌恶记忆形成中连接外周线粒体应激与中枢5-羟色胺神经调节的关键机制。
