Theta-gamma coupling increases during the learning of item-context associations.

Phase-amplitude cross-frequency coupling (CFC) between theta (4-12 Hz) and gamma (30-100 Hz) oscillations occurs frequently in the hippocampus. However, it still remains unclear whether theta-gamma coupling has any functional significance. To address this issue, we studied CFC in local field potential oscillations recorded from the CA3 region of the dorsal hippocampus of rats as they learned to associate items with their spatial context. During the course of learning, the amplitude of the low gamma subband (30-60 Hz) became more strongly modulated by theta phase in CA3, and higher levels of theta-gamma modulation were maintained throughout overtraining sessions. Furthermore, the strength of theta-gamma coupling was directly correlated with the increase in performance accuracy during learning sessions. These findings suggest a role for hippocampal theta-gamma coupling in memory recall.