Recent studies show that higher order oscillatory interactions such as cross-frequency coupling are
important for brain functions that are impaired in schizophrenia, including perception, attention and
memory. Here we investigated the dynamics of oscillatory coupling in the hippocampus of awake rats upon
NMDA receptor blockade by ketamine, a pharmacological model of schizophrenia. Ketamine (25, 50 and
75 mg/kg i.p.) increased gamma and high-frequency oscillations (HFO) in all depths of the CA1-dentate
axis, while theta power changes depended on anatomical location and were independent of a transient
increase of delta oscillations. Phase coherence of gamma and HFO increased across hippocampal layers.
Phase-amplitude coupling between theta and fast oscillations was markedly altered in a dose-dependent
manner: ketamine increased hippocampal theta-HFO coupling at all doses, while theta-gamma coupling
increased at the lowest dose and was disrupted at the highest dose. Our results demonstrate that ketamine
alters network interactions that underlie cognitively relevant theta-gamma coupling