Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv(+) fast-spiking interneurons in mouse and human. We identify AnkR-associated protein complexes including cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). We show that loss of AnkR from forebrain interneurons reduces and disrupts PNNs, decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv(+) fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K+ channels. We identify a novel AnkR-binding motif in Kv3.1b, and show that AnkR is both necessary and sufficient for Kv3.1b membrane localization in interneurons and at nodes of Ranvier. Thus, AnkR regulates Pv(+) fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying beta 1 spectrin-based cytoskeleton.

Automated summary

AnkR is highly enriched in Pv(+) fast-spiking interneurons in mice and humans, and is associated with cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). Loss of AnkR leads to disruption of PNNs, decreases in anxiety-like behaviors, and changes in the excitability and firing properties of Pv(+) fast-spiking interneurons, which is accompanied by a reduction in Kv3.1b K+ channels. AnkR plays a crucial role in organizing ion channels, CAMs, and PNNs in interneurons and at nodes of Ranvier.