Ih tunes theta/gamma oscillations and cross-frequency coupling in an in silico CA3 model

• Published in: PloS one Vol. 8; no. 10; p. e76285
• Main Authors: Neymotin, Samuel A, Hilscher, Markus M, Moulin, Thiago C, Skolnick, Yosef, Lazarewicz, Maciej T, Lytton, William W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-10-2013; Public Library of Science (PLoS)
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Brain Waves; CA3 Region, Hippocampal - physiology; Computer Simulation; Coupling; Excitability; Hippocampus; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism; Information flow; Interneurons - drug effects; Interneurons - physiology; Isoforms; Kinases; Membrane potential; Models, Neurological; Multiscale analysis; Neuromodulation; Neurosciences; Oscillations; Permeability; Pharmacology; Physiology; Pyramidal Cells - drug effects; Pyramidal Cells - pathology; Rodents; Second messengers; Theta Rhythm; Theta rhythms; Trends; Tuning; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076285

Ih channels are uniquely positioned to act as neuromodulatory control points for tuning hippocampal theta (4-12 Hz) and gamma (25 Hz) oscillations, oscillations which are thought to have importance for organization of information flow. contributes to neuronal membrane resonance and resting membrane potential, and is modulated by second messengers. We investigated 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 . Our model demonstrated that modulation of pyramidal and basket allows tuning theta and gamma oscillation frequency and amplitude. Pyramidal also controlled cross-frequency coupling (CFC) and allowed shifting gamma generation towards particular phases of the theta cycle, effected via 's ability to set pyramidal excitability. Our model predicts that in vivo neuromodulatory control of allows flexibly controlling CFC and the timing of gamma discharges at particular theta phases.