Regulation of perisomatic synapses from cholecystokinin basket interneurons through NrCAM and Ankyrin B

Abstract

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^flox/flox:EGFP mice. A novel CCK-BC reporter mouse expressing tdTomato (tdT) at the Synuclein-γ (Sncg) 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.