Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.

Abstract

Anxiety occurs in the early stage of cognitive disorders, which can exacerbate cognitive impairment. However, the pathogenesis of this kind of anxiety remains unclear. In this study, we investigated anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout (PS cDKO) mice, a model of progressive cognitive impairment, using behavioral tests and electrophysiological recordings. Disrupted excitatory/inhibitory (E/I) balance was observed in pyramidal neurons (PNs) of the ventral hippocampus (vHPC) CA1 (vCA1) region of PS cDKO mice. Meanwhile, PV + interneurons showed hypoexcitability, associated with increased outward K⁺ currents due to elevated Kv1.1 potassium channel levels. Importantly, genetic or pharmacological inhibition of Kv1.1 restored PV + interneuron activity and reduced anxiety-like behaviors. These findings highlight a role of Kv1.1 in controlling PV + interneuron excitability, suggesting that targeting Kv1.1 in vCA1 PV + interneurons could mitigate anxiety in early-stage cognitive dysfunction.