Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA.
Nature. 2024 Feb;626(8001):1056-1065. doi: 10.1038/s41586-023-06981-x. Epub 2023 Dec 20.
The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs. The human EC continues to develop during childhood, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5RELN inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5RELN cells. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.
人脑的颞叶包含内嗅皮层(entorhinal cortex,EC)。大脑的这一区域是一个高度相互连接的感觉和空间信息综合中枢;它在情景记忆形成中也起着关键作用,是皮质海马传入的主要来源。人类的 EC 在儿童期继续发育,但神经发生和神经元迁移到 EC 被广泛认为在出生时就已完成。在这里,我们发现人类颞叶中有许多年轻的神经元迁移到出生后的 EC 和邻近区域,其中一个大的切线流持续到大约 1 岁,放射状分散持续到大约 2 到 3 岁。相比之下,我们在恒河猴(Macaca mulatta)中没有发现类似的出生后迁移。神经节隆起生发区、EC 流和出生后 EC 的免疫染色和单细胞 RNA 测序表明,EC 流中的大多数迁移细胞来自尾侧神经节隆起,并成为 LAMP5RELN 抑制性中间神经元。这些迟来的中间神经元可能会在儿童积极与环境互动的时期,继续塑造感觉和空间信息的处理。EC 是大脑中最早受到阿尔茨海默病影响的区域之一,之前的工作已经将认知能力下降与 LAMP5RELN 细胞的丧失联系起来。我们的研究表明,这些细胞中的许多是通过儿童早期的一个主要出生后迁移流到达 EC 的。