Lymer Seana, Patel Keyur, Lennon Jennifer, Blau Justin
bioRxiv. 2024 May 26:2024.05.25.595887. doi: 10.1101/2024.05.25.595887.
s-LNv circadian pacemaker neurons show dramatic structural plasticity, with their projections expanded at dawn and then retracted by dusk. This predictable plasticity makes s-LNvs ideal to study molecular mechanisms of plasticity. Although s-LNv plasticity is controlled by their molecular clock, changing s-LNv excitability also regulates plasticity. Here, we tested the idea that s-LNvs use activity-regulated genes to control plasticity. We found that inducing expression of either of the activity-regulated transcription factors Hr38 or Sr (orthologs of mammalian Nr4a1 and Egr1) is sufficient to rapidly expand s-LNv projections. Conversely, transiently knocking down expression of either or blocks expansion of s-LNv projections at dawn. We show that Hr38 rapidly induces transcription of which encodes a Rac1 GEF required for s-LNv plasticity rhythms. We conclude that the s-LNv molecular clock controls s-LNv excitability, which couples to an activity-regulated gene expression program to control s-LNv plasticity.
小侧神经元（s-LNv）生物钟起搏器神经元表现出显著的结构可塑性，其投射在黎明时扩展，然后在黄昏时缩回。这种可预测的可塑性使小侧神经元成为研究可塑性分子机制的理想对象。虽然小侧神经元的可塑性受其分子时钟控制，但改变小侧神经元的兴奋性也能调节可塑性。在这里，我们测试了小侧神经元利用活动调节基因来控制可塑性的观点。我们发现，诱导活动调节转录因子Hr38或Sr（哺乳动物Nr4a1和Egr1的直系同源物）中的任何一个表达，足以迅速扩展小侧神经元的投射。相反，瞬时敲低Hr38或Sr的表达会阻断黎明时小侧神经元投射的扩展。我们表明，Hr38能迅速诱导Pbl的转录，Pbl编码小侧神经元可塑性节律所需的一种Rac1鸟苷酸交换因子（GEF）。我们得出结论，小侧神经元分子时钟控制小侧神经元的兴奋性，兴奋性与一个活动调节基因表达程序相结合，以控制小侧神经元的可塑性。
