I_h, GIRK, and KCNQ/Kv7 channels differently modulate sharp wave - ripples in the dorsal and ventral hippocampus

Sharp waves and ripples (SPW-Rs) are endogenous transient patterns of hippocampus local network activity implicated in several functions including memory consolidation, and they are diversified between the dorsal and the ventral hippocampus. Ion channels in the neuronal membrane play important roles in cell and local network function. In this study, using transverse slices and field potential recordings from the CA1 field of rat hippocampus we show that GIRK and KCNQ2/3 potassium channels play a higher role in modulating SPW-Rs in the dorsal hippocampus, while I_h and other KCNQ (presumably KCNQ5) channels, contribute to shaping SPW-R activity more in the ventral than in dorsal hippocampus. Specifically, blockade of I_h channels by ZD 7288 reduced the rate of occurrence of SPW-Rs and increased the generation of SPW-Rs in the form of clusters in both hippocampal segments, while enhanced the amplitude of SPW-Rs only in the ventral hippocampus. Most effects of ZD 7288 appeared to be independent of NMDA receptors' activity. However, the effects of blockade of NMDA receptors depended on the functional state of I_h channels in both hippocampal segments. Blockade of GIRK channels by Tertiapin-Q increased the rate of occurrence of SPW-Rs only in the dorsal hippocampus and the probability of clusters in both segments of the hippocampus. Blockade of KCNQ2/3 channels by XE 991 increased the rate of occurrence of SPW-Rs and the probability of clusters in the dorsal hippocampus, and only reduced the clustered generation of SPW-Rs in the ventral hippocampus. The blocker of KCNQ1/2 channels, that also enhances KCNQ5 channels, UCL 2077, increased the probability of clusters and the power of the ripple oscillation in the ventral hippocampus only. These results suggest that GIRK, KCNQ and I_h channels represent a key mechanism for modulation of SPW-R activity which act differently in the dorsal and ventral hippocampus, fundamentally supporting functional diversification along the dorsal-ventral axis of the hippocampus.