I(h) Tunes Theta/Gamma Oscillations and Cross-Frequency Coupling In an In Silico CA3 Model

[Image: see text] channels are uniquely positioned to act as neuromodulatory control points for tuning hippocampal theta (4–12 Hz) and gamma ([Image: see text]25 Hz) oscillations, oscillations which are thought to have importance for organization of information flow. [Image: see text] contributes to neuronal membrane resonance and resting membrane potential, and is modulated by second messengers. We investigated [Image: see text] oscillatory control using a multiscale computer model of hippocampal CA3, where each cell class (pyramidal, basket, and oriens-lacunosum moleculare cells), contained type-appropriate isoforms of [Image: see text]. Our model demonstrated that modulation of pyramidal and basket [Image: see text] allows tuning theta and gamma oscillation frequency and amplitude. Pyramidal [Image: see text] also controlled cross-frequency coupling (CFC) and allowed shifting gamma generation towards particular phases of the theta cycle, effected via [Image: see text] 's ability to set pyramidal excitability. Our model predicts that in vivo neuromodulatory control of [Image: see text] allows flexibly controlling CFC and the timing of gamma discharges at particular theta phases.