Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States.
Mortimer B Zuckerman Mind Brain Behavior Institute, Department of Neuroscience, Columbia University, New York, United States.
Elife. 2021 May 11;10:e67510. doi: 10.7554/eLife.67510.
The mechanisms specifying neuronal diversity are well characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts) and identify them in a synapse-scale TEM reconstruction of the larval central nervous system. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohorts share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.
神经元多样性的形成机制已经得到了很好的描述，但目前尚不清楚这些机制是如何调节神经回路组装的。为了解决这个问题，我们绘制了来自七个双侧神经前体细胞（神经母细胞）的 160 个中间神经元的发育起源，并在幼虫中枢神经系统的突触尺度 TEM 重建中对其进行了鉴定。我们发现，谱系通过以 Notch 依赖性的方式产生感觉和运动半谱系，同时构建感觉和运动神经丛。半谱系中的神经元在神经丛中共享共同的突触靶向，进一步基于神经元的时间身份进行细化。连接组分析表明，半谱系-时间群体具有共同的连接性。最后，我们表明，仅仅是接近度不能解释观察到的连接结构，这表明半谱系/时间身份赋予了额外的特异性。因此，我们证明了指定神经元多样性的机制也控制着电路的形成和功能，并且这些原则在整个神经系统中具有广泛的适用性。
