H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast spiking

Histamine-containing neurons of the tuberomammilary nucleus project to the hippocampal formation to innervate H-1 and H-2 receptors on both principal and inhibitory interneurons. Here we show that H-2 receptor activation negatively modulates outward currents through Kv3.2-containing potassium channels by a mechanism involving PKA phosphorylation in inhibitory interneurons. PKA phosphorylation of Kv3.2 lowered the maximum firing frequency of inhibitory neurons, which in turn negatively modulated high-frequency population oscillations recorded in principal cell layers. All these effects were absent in a Kv3.2 knockout mouse. These data reveal a novel pathway for histamine-dependent regulation of high-frequency oscillations within the hippocampal formation.