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bioRxiv · 10.1101/2024.11.04.621872

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

Oldre, E. N.·Webb, B. D.·Sperringer, J.·Maness, P. F.
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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:Ank2flox/flox:EGFP mice. A novel CCK-BC reporter mouse expressing tdTomato (tdT) at the Synuclein-{gamma} (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.

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Oldre, E. N., Webb, B. D., Sperringer, J., Maness, P. F.. 2024-11-04. Perisomatic Synaptic Targeting by Cholecystokinin-Basket Interneurons through NrCAM and Ankyrin B. https://doi.org/10.1101/2024.11.04.621872

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