PDF(Pubmed)
Abstract：
The patterns of synaptic connectivity and physiological properties of diverse neuron types are shaped by distinct gene sets. Our study demonstrates that, in the mouse forebrain, the transcriptional profiles of inhibitory GABAergic interneurons are regulated by Nr4a1, an orphan nuclear receptor whose expression is transiently induced by sensory experiences and is required for normal learning. Nr4a1 exerts contrasting effects on the local axonal wiring of parvalbumin- and somatostatin-positive interneurons, which innervate different subcellular domains of their postsynaptic partners. The loss of Nr4a1 activity in these interneurons results in bidirectional, cell-type-specific transcriptional switches across multiple gene families, including those involved in surface adhesion and repulsion. Our findings reveal that combinatorial synaptic organizing codes are surprisingly flexible and highlight a mechanism by which inducible transcription factors can influence neural circuit structure and function.
摘要：
不同神经元类型的突触连接模式和生理特性由不同的基因集形成。我们的研究表明,在老鼠的前脑，抑制性GABA能中间神经元的转录谱受Nr4a1调节，Nr4a1是一种孤儿核受体，其表达是由感觉经验短暂诱导的，是正常学习所必需的。Nr4a1对小白蛋白和生长抑素阳性中间神经元的局部轴突布线产生对比作用，神经支配其突触后伴侣的不同亚细胞结构域。这些中间神经元中Nr4a1活性的丧失导致双向，跨多个基因家族的细胞类型特异性转录转换，包括那些涉及表面粘附和排斥。我们的发现表明，组合突触组织代码具有惊人的灵活性，并突出了诱导型转录因子可以影响神经回路结构和功能的机制。
