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-氨基丁酸能（GABA）神经元的胚胎发生时序对其功能特化至关重要。在新生海马体中，最早诞生的GABA细胞（ebGABAs）可通过协调群体同步活动发挥“枢纽”作用。然而，这类细胞在成年后的命运仍鲜为人知。为填补这一研究空白，我们联合运用电生理学、神经化学分析、光遗传连接图谱绘制技术，以及离体和在体钙成像手段，对海马CA1区的ebGABAs展开了研究。我们发现，海马CA1区的ebGABAs不仅在发育阶段承担枢纽功能，还始终保持独特的形态生理特征与连接组特征，包括对长程投射靶点和局部兴奋性输入的偏好性。在体实验中，ebGABAs在动物运动时被激活，与CA1细胞集群活动高度相关，并展现出极强的功能连接性。由此可见，ebGABAs从诞生之初即已完成功能特化，以保障其在整个生命周期中发挥独特功能。在成年大脑中，这类细胞可通过协调远隔脑区的细胞集群活动，发挥长程枢纽作用。