再生神经科学的一个核心问题是合成神经回路,比如由两个物种建造的,可以在完整的大脑中发挥作用。这里,我们应用胚泡互补来选择性地建立和测试种间神经回路。尽管经历了大约一两千万年的进化,以及大脑大小的显著物种差异,注射到小鼠囊胚中的大鼠多能干细胞在整个小鼠大脑中发育并持续存在。出乎意料的是,小鼠小生境重新编程大脑皮层和海马中大鼠神经元的出生日期,支持大鼠-小鼠突触活动。当小鼠嗅觉神经元被基因沉默或杀死时,大鼠神经元将信息流恢复到气味处理电路。此外,他们拯救了寻找食物的原始行为,虽然不如小鼠神经元好。通过揭示老鼠可以使用来自另一个物种的神经元来感知世界,我们建立神经胚泡互补作为一个强大的工具来识别大脑发育的保守机制,可塑性,和修复。
A central question for regenerative neuroscience is whether synthetic neural circuits, such as those built from two species, can function in an intact brain. Here, we apply blastocyst complementation to selectively build and test interspecies neural circuits. Despite approximately 10-20 million years of evolution, and prominent species differences in brain size, rat pluripotent stem cells injected into mouse blastocysts develop and persist throughout the mouse brain. Unexpectedly, the mouse niche reprograms the birth dates of rat neurons in the cortex and hippocampus, supporting rat-mouse synaptic activity. When mouse olfactory neurons are genetically silenced or killed, rat neurons restore information flow to odor processing circuits. Moreover, they rescue the primal behavior of food seeking, although less well than mouse neurons. By revealing that a mouse can sense the world using neurons from another species, we establish neural blastocyst complementation as a powerful tool to identify conserved mechanisms of brain development, plasticity, and repair.