Perisomatic Synaptic Targeting by Cholecystokinin-Basket Interneurons through NrCAM and Ankyrin B

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 prefrontal cortex (PFC). Immunolabeling of CCK-BC terminals for vesicular glutamate transporter-3 (VGlut3) or vesicular glutamate 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:Ank2flox/flox:EGFP mice. A novel CCK-BC reporter mouse expressing tdTomato (tdT) at the Synuclein-γ (Sncg) locus showed NCAM localized to presynaptic Sncg+ CCK-BCs, as well as to postsynaptic PN soma of WT mice. Results implicate NrCAM homophilic interactions and Ankyrin B binding with development of inhibitory connectivity between CCK-BCs and excitatory neurons of the PFC.