Early-life experience influences subsequent maturation and function of the adult brain, sometimes even in a sex-specific manner, but underlying molecular mechanisms are poorly understood. We describe here how juvenile experience defines sexually dimorphic synaptic connectivity in the adult Caenorhabditis elegans nervous system. Starvation of juvenile males disrupts serotonin-dependent activation of the CREB transcription factor in a nociceptive sensory neuron, PHB. CREB acts through a cascade of transcription factors to control expression of an atypical cadherin protein, FMI-1/Flamingo/CELSR. During postembryonic development, FMI-1 promotes and maintains synaptic connectivity of PHB to a command interneuron, AVA, in both sexes, but a serotonin-dependent transcriptional regulatory cassette antagonizes FMI-1 expression in males, thereby establishing sexually dimorphic connectivity between PHB and AVA. A critical regulatory node is the CREB-target LIN-29, a Zn finger transcription factor that integrates four layers of information: sexual specificity, past experience, time and cell-type specificity. Our findings provide the mechanistic details of how an early juvenile experience defines sexually dimorphic synaptic connectivity.

中文翻译：

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由性别特异性钙粘蛋白表达定义的经验依赖性、性二态性突触连接


早期生活经历会影响成人大脑的后续成熟和功能，有时甚至以性别特异性的方式影响，但对潜在的分子机制知之甚少。我们在这里描述了青少年经历如何定义成人秀丽隐杆线虫神经系统中的性二态突触连接。幼年雄性饥饿会破坏伤害性感觉神经元 PHB 中 CREB 转录因子的血清素依赖性激活。CREB 通过级联转录因子发挥作用，以控制非典型钙粘蛋白 FMI-1/Flamingo/CELSR 的表达。在胚胎后发育过程中，FMI-1 促进并维持 PHB 与两性指令中间神经元 AVA 的突触连接，但 5-羟色胺依赖性转录调节盒拮抗男性 FMI-1 表达，从而在 PHB 和 AVA 之间建立性二态连接。一个关键的调节节点是 CREB 靶标 LIN-29，这是一种 Zn 指转录因子，整合了四层信息：性特异性、既往经历、时间和细胞类型特异性。我们的研究结果提供了早期青少年经历如何定义性二态突触连接的机制细节。