Effects of XE991, retigabine, losigamone and ZD7288 on kainate-induced theta-like and gamma network oscillations in the rat hippocampus in vitro

Abstract

Ion currents such as M-currents (I(M)), persistent sodium currents (I(NaP)) and H-currents (I(h)) have been observed in a variety of brain regions, including the hippocampal formation, where storage and retrieval of information are facilitated by oscillatory network activities. They have been suggested to play an important role in neuronal excitability, synaptic transmission, membrane oscillatory activity, and in shaping resonance. Resonance and membrane potential oscillations have been implied in the generation of theta but not gamma oscillations. Here, we performed extracellular field potential recordings in hippocampal slices from adult rats and applied either the I(M) blocker XE991, the I(M) activator retigabine, the I(NaP) blocker losigamone or the I(h) inhibitor ZD7288 to test if these currents contribute to the generation of network oscillations. Kainate application induced network theta-like frequency oscillations in coronal slices as well as network gamma frequency oscillations in horizontal slices, and these remained stable for up to 3h. Power spectrum analysis revealed that all agents dose-dependently reduced the network oscillations in both frequency bands in areas CA3 and CA1. In contrast, the peak oscillation frequency was affected differentially. These results confirm that theta-like frequency oscillations are induced in longitudinal slices while gamma frequency oscillations dominate in horizontal slices. They also suggest that modifying neuronal excitability and transmitter release alters hippocampal network oscillations which are thought to be crucial for memory processing.