Reduced Kv3.1 Activity in Dentate Gyrus Parvalbumin Cells Induces Vulnerability to Depression

Abstract Parvalbumin (PV)-expressing interneurons are important for cognitive and emotional behaviors. These neurons express high level of p11, a protein associated with depression and action of antidepressants. Here we show that either specific deletion of p11 (p11 cKO) or chemogenetic inhibition in dentate gyrus (DG) PV neurons leads to anxiety-like behavior and susceptibility to depression in mice. DG PV neurons from p11 cKO mice showed reduced level and function of Kv3.1, and consequentially reduced capacity of high-frequency firing and altered short-term plasticity at synapses on granule cells. Activation of Kv3.1 or overexpression of the channel attenuated the vulnerability to depressive behavior.