High-frequency oscillation in the hippocampus of the behaving rat and its modulation by the histaminergic system.

The histaminergic neurons located in the posterior hypothalamus modulate whole brain activity in a manner dependent on behavioral state. We have investigated their influence on high-frequency oscillation (200-Hz ripples) in the hippocampal CA1 region of freely moving rats. The occurrence of these ripples, assumed to be involved in memory trace formation, was markedly enhanced after injection of the H1-antagonists pyrilamine and ketotifen in a lateral ventricle, indicating a tonic activity of the histaminergic system. The H2- and H3-antagonists cimetidine and thioperamide were ineffective. We suggest a mediation of these effects through blocking the known histaminergic excitation of septal neurons. Histamine administered by the intracerebroventricular route had an inhibitory action on ripples. H1-receptor activation, which has been shown to inhibit learning and memory, thus shifts hippocampal activity away from high-frequency oscillation toward theta activity.