Oldre Erik N, Webb Barrett D, Sperringer Justin E, Maness Patricia F
Department of Biochemistry and Biophysics, CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
Curr Res Neurobiol. 2025 Apr 8;8:100150. doi: 10.1016/j.crneur.2025.100150. eCollection 2025 Jun.
The perisomatic region of cortical pyramidal neurons (PNs) integrates local and long-range inputs and regulates firing. This domain receives GABAergic inputs from cholecystokinin (CCK)- and Parvalbumin (PV)-expressing basket cells (BCs) but how synaptic contacts are established is unclear. Neuron-glial related cell adhesion molecule (NrCAM) is a homophilic transmembrane protein that binds the scaffold protein Ankyrin B. Here we show that NrCAM and Ankyrin B mediate perisomatic synaptic contact between CCK-BCs and PNs in mouse medial prefrontal cortex (mPFC). Immunolabeling of CCK-BC terminals for vesicular glutamate transporter-3 (VGLUT3) or vesicular GABA transporter (VGAT) revealed a significant decrease in CCK-BC synaptic puncta on PN soma in NrCAM-null mice, however no decrease in PV-BC puncta or cell loss. VGLUT3+ CCK-BC puncta were also decreased by Ankyrin B deletion from PNs in Nex1Cre-ERT2:Ank2:EGFP mice. A novel CCK-BC reporter mouse expressing tdTomato (tdT) at the Synuclein-γ () locus showed NrCAM localized to Sncg + CCK-BCs, and to postsynaptic PN soma in Nex1Cre-ERT2:Ank2:EGFP mice. Results suggest that NrCAM and Ankyrin B contribute to the establishment of connectivity between CCK-BCs and excitatory neurons of the mPFC.
皮质锥体神经元（PNs）的胞体周围区域整合局部和远距离输入并调节放电。该区域接收来自表达胆囊收缩素（CCK）和小白蛋白（PV）的篮状细胞（BCs）的GABA能输入，但尚不清楚突触接触是如何建立的。神经元-胶质细胞相关细胞粘附分子（NrCAM）是一种同源跨膜蛋白，可与支架蛋白锚蛋白B结合。在这里，我们表明NrCAM和锚蛋白B介导小鼠内侧前额叶皮质（mPFC）中CCK-BCs与PNs之间的胞体周围突触接触。用囊泡谷氨酸转运体-3（VGLUT3）或囊泡GABA转运体（VGAT）对CCK-BC终末进行免疫标记显示，在NrCAM基因敲除小鼠中，PNs胞体上CCK-BC突触小体显著减少，但PV-BC突触小体或细胞丢失没有减少。在Nex1Cre-ERT2:Ank2:EGFP小鼠中，通过从PNs中删除锚蛋白B，VGLUT3+ CCK-BC突触小体也减少了。一种在突触核蛋白-γ（）位点表达tdTomato（tdT）的新型CCK-BC报告小鼠显示，NrCAM定位于Sncg + CCK-BCs以及Nex1Cre-ERT2:Ank2:EGFP小鼠的突触后PNs胞体。结果表明，NrCAM和锚蛋白B有助于建立mPFC中CCK-BCs与兴奋性神经元之间的连接。
