The basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.

中文翻译：

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细胞的出生日期可预测前脑的层状和区域性胆碱能投射地形

基底前脑胆碱能系统广泛分布于整个皮层，是引起觉醒和注意的神经调节的重要来源。传统上，该系统被认为具有分散的功能。但是，最近的研究表明胆碱能信号传导具有高度的时空特异性。胆碱能传入者的组织如何赋予这种精确度仍然未知。在这里，使用交叉遗传命运映射，我们证明了皮质内的胆碱能纤维表现出显着的层流和区域特异性，并且这是根据细胞的出生日期而组织的。令人惊讶的是，皮质内先天性胆碱能投射遵循由内而外的神经支配模式。虽然早期出生的胆碱能人群针对的是深层，晚出生的人神经支配浅表层。我们还发现生日可以预测杏仁核，海马和前额叶皮层内的胆碱能神经支配模式。我们的工作揭示了胆碱能系统内以前未知的特异性以及组装这些电路的发展逻辑。