Cold Spring Harbor Laboratory, Cold Spring Harbor, United States.
Program in Neurobiology, Stony Brook University, Stony Brook, United States.
Elife. 2024 Jul 16;13:RP93481. doi: 10.7554/eLife.93481.
Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remain poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage () and molecular (, ) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta, and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal, and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.
轴突-轴突型细胞（Axo-axonic cells，AACs），在大脑皮层中也被称为 Chandelier 细胞（ChCs），是新皮层、海马体和基底外侧杏仁核（basolateral amygdala，BLA）中描述的最独特的 GABA 能中间神经元类型。AACs 选择性地在其轴突起始段（axon initial segment，AIS）上支配谷氨酸能投射神经元（projection neurons，PNs），因此可能对 PNs 的爆发活动施加决定性的控制，并调节 PNs 的功能集合。然而，AACs 的全脑分布、突触连接和回路功能仍然知之甚少，这主要是由于缺乏特异性和可靠的实验工具。在这里，我们建立了一种交叉遗传策略，该策略基于其谱系（lineage）和分子（molecular）标记，实现了整个小鼠大脑中 AACs 的特异性和全面靶向。我们发现 AACs 广泛分布于几乎所有的皮层衍生结构中，不仅包括背侧皮层衍生的新皮层和内侧皮层衍生的海马体结构，还包括外侧皮层衍生的屏状核-岛叶复合体，以及腹侧皮层衍生的扩展杏仁核复合体和嗅觉中心。AACs 在嗅前核、穹窿和外侧隔室中也很丰富。AACs 在新皮层区域和层以及海马体结构的亚区之间的密度表现出特征性的变化。新皮层 AACs 包含具有不同树突和轴突分支模式的多个层型亚型。从 AAC 到新皮层、海马体和 BLA 区域的逆行单突触示踪显示出共享和独特的突触输入模式。AACs 的特异性和全面靶向促进了对其跨脑结构的发育遗传程序和回路功能的研究，为理解真正的细胞类型在脑区和物种之间的保守性和变异性提供了一个真实的平台。
