Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
MRC BNDU, University of Oxford, Oxford OX1 3TH, UK.
Cell Rep. 2021 Apr 27;35(4):109041. doi: 10.1016/j.celrep.2021.109041.
Synaptic circuits in the brain are precisely organized, but the processes that govern this precision are poorly understood. Here, we explore how distinct embryonic neural progenitor pools in the lateral ganglionic eminence contribute to neuronal diversity and synaptic circuit connectivity in the mouse striatum. In utero labeling of Tα1-expressing apical intermediate progenitors (aIP), as well as other progenitors (OP), reveals that both progenitors generate direct and indirect pathway spiny projection neurons (SPNs) with similar electrophysiological and anatomical properties and are intermingled in medial striatum. Subsequent optogenetic circuit-mapping experiments demonstrate that progenitor origin significantly impacts long-range excitatory input strength, with medial prefrontal cortex preferentially driving aIP-derived SPNs and visual cortex preferentially driving OP-derived SPNs. In contrast, the strength of local inhibitory inputs among SPNs is controlled by birthdate rather than progenitor origin. Combined, these results demonstrate distinct roles for embryonic progenitor origin in shaping neuronal and circuit properties of the postnatal striatum.
大脑中的突触回路组织精确，但控制这种精确性的过程还知之甚少。在这里，我们探讨了外侧神经节隆起中的不同胚胎神经前体细胞池如何有助于小鼠纹状体中神经元多样性和突触回路连接。对表达 Tα1 的顶侧中间祖细胞（aIP）以及其他祖细胞（OP）的体内标记显示，这两种祖细胞都产生具有相似电生理和解剖特性的直接和间接通路棘突投射神经元（SPN），并在纹状体中部混合。随后的光遗传回路映射实验表明，祖细胞的起源显著影响长程兴奋性输入强度，内侧前额叶皮层优先驱动 aIP 衍生的 SPN，而视觉皮层优先驱动 OP 衍生的 SPN。相比之下，SPN 之间局部抑制性输入的强度受出生时间而不是祖细胞起源的控制。总的来说，这些结果表明胚胎祖细胞起源在塑造出生后纹状体的神经元和回路特性方面发挥了不同的作用。
