Calculated diameters of OLM dendritic segments.

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo, and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed, and make available several key data sets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The data set includes detailed scanning electron microscopy (SEM)-based 3D reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core data set with other anatomical data, patch-clamp electrophysiology, and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For example, we estimated that an OLM cell receives about 8,400, whereas an HS cell about 15,600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.

γ-氨基丁酸能抑制性神经元（GABAergic inhibitory neurons）从根本上塑造大脑皮层环路的活动与可塑性。这类神经元的一个主要亚群以表达生长抑素（Somatostatin, SOM）为特征，此类细胞在包括海马在内的多个脑区的神经可塑性、学习与记忆过程中发挥关键作用，且与多种神经精神疾病及神经退行性疾病密切相关。海马CA1区中两类主要的表达生长抑素的细胞分别为奥利昂-拉克努萨姆-分子层（oriens-lacunosum-moleculare, OLM）细胞与海马-隔核（hippocampo-septal, HS）细胞，这两类细胞在胞体-树突形态结构上存在诸多相似之处，但轴突靶向区域各异，在体活动模式不同，且被认为具备截然不同的网络功能。然而，要全面阐明这类中间神经元的功能角色，需要精准描述其内在计算特性与突触相互作用机制。在本研究中，我们生成、分析并公开了多组核心数据集，可用于定量比较小鼠OLM细胞与HS细胞的多项解剖学与生理学特性。本数据集包含基于扫描电子显微镜（scanning electron microscopy, SEM）的OLM细胞与HS细胞及其兴奋性、抑制性突触输入的精细三维重建结果，结合该核心数据集与其他解剖学数据、膜片钳电生理学（patch-clamp electrophysiology）技术及神经元隔室建模（compartmental modeling）方法，我们解析了此类细胞的精确形态结构、突触输入、输出模式与基本生理特性。本研究结果揭示了OLM细胞与HS细胞之间的关键差异，尤其体现在突触输入与线粒体的密度及分布模式上，例如我们测算得出单个OLM细胞接收约8400个突触输入，而单个HS细胞接收约15600个突触输入，其中约16%为γ-氨基丁酸能突触输入。本研究的数据与模型为阐明OLM细胞与HS细胞的功能差异提供了新的理论依据，同时为构建此类神经元及海马环路的更精细功能模型提供了关键支撑。