Hippocampal hub neurons maintain distinct connectivity throughout their lifetime

The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.大脑皮层γ-氨基丁酸（GABA）神经元的胚胎发育时序起源，对其功能特化至关重要。在新生海马体中，诞生最早的GABA能神经元（ebGABAs）通过协调群体同步活动，充当“枢纽”角色。然而，这类神经元在成年个体中的最终命运仍鲜为人知。为填补这一研究空白，我们结合电生理记录、神经化学分析、光遗传学连接组测绘，以及离体和在体钙成像技术，对CA1区ebGABAs展开了研究。结果表明，CA1区ebGABAs不仅在发育阶段发挥枢纽作用，还维持着独特的形态生理与连接组特征，包括对远距离投射靶点和局部兴奋性输入的倾向性。在体实验中，ebGABAs在动物运动时被激活，与CA1区细胞集群活动高度相关，并展现出较强的功能连接性。由此可见，ebGABAs从诞生之初就已被赋予特定属性，以保障其在整个生命周期中发挥独特功能。在成年大脑中，这类神经元可能通过协调远距离脑区的细胞集群活动，承担起远距离枢纽的功能角色。