Department of Neuroscience, The Scripps Research Institute, La Jolla, San Diego, CA, USA; Neuroscience Graduate Program, University of California, San Diego, La Jolla, San Diego, CA, USA.
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cell. 2024 Apr 25;187(9):2143-2157.e15. doi: 10.1016/j.cell.2024.03.042.
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.
对于再生神经科学来说，一个核心问题是，由两个物种构建的合成神经回路，是否能够在完整的大脑中发挥作用。在这里，我们应用胚泡互补来有选择地构建和测试种间神经回路。尽管存在大约 1000 万至 2000 万年的进化差异，以及大脑大小方面显著的物种差异，但注入到小鼠胚泡中的大鼠多能干细胞在整个小鼠大脑中发育并持续存在。出人意料的是，小鼠小生境将大鼠神经元的出生日期重新编程到皮质和海马体中，支持大鼠-小鼠突触活动。当小鼠嗅球神经元被基因沉默或杀死时，大鼠神经元恢复到气味处理回路的信息流。此外，它们挽救了觅食的原始行为，尽管不如小鼠神经元那么好。通过揭示一只老鼠可以使用另一种物种的神经元来感知世界，我们确立了神经胚泡互补作为一种强大的工具，可以识别大脑发育、可塑性和修复的保守机制。
