Cell-type-specific contributions to theta-gamma coupled rhythms in the hippocampus.

Abstract

Distinct inhibitory cell types participate in cognitively relevant nested brain rhythms, and particular changes in such rhythms are known to occur in disease states. Specifically, the coexpression of theta and gamma rhythms in the hippocampus is believed to represent a general coding scheme, but cellular-based generation mechanisms for these coupled rhythms are currently unclear. We develop a population rate model of the CA1 hippocampus that encompasses circuits of three inhibitory cell types (bistratified cells and parvalbumin [PV]-expressing and cholecystokinin [CCK]-expressing basket cells) and pyramidal cells to examine this. We constrain parameters and perform numerical and theoretical analyses. The theory, in combination with the numerical explorations, predicts circuit motifs and specific cell-type mechanisms that are essential for the coexistence of theta and gamma oscillations. We find that CCK-expressing basket cells initiate the coupled rhythms and regularize theta, and PV-expressing basket cells enhance both theta and gamma rhythms. Pyramidal and bistratified cells govern the generation of theta rhythms, and PV-expressing basket and pyramidal cells play dominant roles in controlling theta frequencies. Our circuit motifs for the theta-gamma coupled rhythm generation could be applicable to other brain regions.