Cholinergic blockade reduces theta-gamma phase amplitude coupling and speed modulation of theta frequency consistent with behavioral effects on encoding

• Published in: The Journal of neuroscience 2013-12, Vol.33 (50), p.19635-19646
• Main Authors: Newman, Ehren L, Gillet, Shea N, Climer, Jason R, Hasselmo, Michael E
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Entorhinal Cortex - drug effects; Male; Movement - drug effects; Muscarinic Antagonists - pharmacology; Neurons - drug effects; Rats; Rats, Long-Evans; Scopolamine Hydrobromide - pharmacology; Theta Rhythm - drug effects
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.2586-13.2013

Large-scale neural activation dynamics in the hippocampal-entorhinal circuit local field potential, observable as theta and gamma rhythms and coupling between these rhythms, is predictive of encoding success. Behavioral studies show that systemic administration of muscarinic acetylcholine receptor antagonists selectively impairs encoding, suggesting that they may also disrupt the coupling between the theta and gamma bands. Here, we tested the hypothesis that muscarinic antagonists selectively disrupt coupling between theta and gamma. Specifically, we characterized the effects of systemically administered scopolamine on movement-induced theta and gamma rhythms recorded in the superficial layers of the medial entorhinal cortex (MEC) of freely moving rats. We report the novel result that gamma power at the peak of theta was most reduced following muscarinic blockade, significantly shifting the phase of maximal gamma power to occur at later phases of theta. We also characterize the existence of multiple distinct gamma bands in the superficial layers of the MEC. Further, we observed that theta frequency was significantly less modulated by movement speed following muscarinic blockade. Finally, the slope relating speed to theta frequency, a correlate of familiarity with a testing enclosure, increased significantly less between the preinjection and recovery trials when scopolamine was administered during the intervening injection session than when saline was administered, suggesting that scopolamine reduced encoding of the testing enclosure. These data are consistent with computational models suggesting that encoding and retrieval occur during the peak and trough of theta, respectively, and support the theory that acetylcholine regulates the balance between encoding versus retrieval.