Inhibitory control of intrinsic hippocampal oscillations?

Abstract

An oscillatory mode of activity is a basic operational mode of the hippocampus. Such activity involves the concurrent expression of several rhythmic processes, of which theta (4–15 Hz) and gamma (20–80 Hz) oscillations are prominent and considered to be important for cognitive processing. In an experimental model that preserves the intrinsic network oscillator, exhibiting the dependency on cholinergic inputs and consequent expression of concurrent theta and gamma oscillations, we investigate the intrinsic mechanisms underlying such integrated hippocampal network responses. This experimental framework is used here to examine the currently prevailing dogma, that interneurons control hippocampal oscillations. The spontaneous response of individual pyramidal cells (in areas CA3 and CA1) and interneurons (area CA3), during oscillatory activity, was monitored intracellularly. Particular attention was given to the initiation of interneuron discharge during oscillations, to the impact of the synaptic output of discharging interneurons on the oscillatory activity, and to the time at which interneurons discharge in relation to the oscillatory cycles. Analysis of the spontaneous patterns of activity in individual interneurons and their outcome, during the oscillatory activity, revealed that interneuron activity is incompatible with initiating, pacing or determining the oscillatory frequencies, although contributing to the apparent rhythmic patterns. Moreover, our results show that non-interneuronal members of the network control interneuron activity. We therefore suggest that the activity of the excitatory cells, i.e., principle cells, is critical toward the initiation, pacing and synchronization of intrinsic hippocampal network oscillations.