Do Septal Neurons Pace the Hippocampal Theta Rhythm?

The hippocampal theta rhythm (rhythmical slow activity, RSA) is one of the most thoroughly studied EEG phenomena. Much of this experimental interest has been stimulated by suggestions that the mnemonic functions of the hippocampus may depend upon theta-related neuronal activity. Inputs from the medial septal nuclei to the hippocampus were shown to be essential for the theta rhythm in the 1950s, but the role of these basal forebrain projections has not been clearly defined. Four models of the septo-hippocampal connections involved in theta rhythm production are reviewed as the precise roles of these projections are discussed. In our final, consolidated model both cholinergic and GABAergic septal projection cells fire in rhythmic bursts that entrain hippocampal interneurons. The resulting rhythmic inhibition of hippocampal projection cells, together with their excitatory interconnections, generates at least one component of the theta rhythm.