Cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain
Cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain
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DOI：
10.7554/elife.63249
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发表时间：
2020-12-23
期刊：
影响因子：
7.7
通讯作者：
Fishell G
中科院分区：
文献类型：
--
作者：
Allaway KC;Muñoz W;Tremblay R;Sherer M;Herron J;Rudy B;Machold R;Fishell G
基底前脑胆碱能系统广泛地投射到整个皮层，并构成唤醒和注意力的神经调节的关键来源。传统上，这个系统被认为是分散的。然而，最近的研究表明胆碱能信号具有高度的时空特异性。胆碱能传入神经的组织如何赋予这种精确度仍然是未知的。在这里，使用交叉遗传命运映射，我们表明，小鼠皮质内的胆碱能纤维表现出显着的层状和区域特异性，这是根据细胞的出生日期。引人注目的是，大脑皮层中与生俱来的胆碱能投射遵循一种由内而外的神经支配模式。早期出生的胆碱能神经群体主要分布于深层，晚期出生的胆碱能神经群体主要分布于浅层。我们还发现，出生日期可以预测杏仁核、海马和前额皮质内的胆碱能神经支配模式。我们的工作揭示了胆碱能系统和这些电路组装的发展逻辑中以前未被重视的特异性。
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 mouse 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.