Date of Completion
Chi-Ming Chen, Deborah Fein, James Chrobak
Field of Study
Master of Science
Disrupted neuronal oscillations have been identified as a potentially important biomarker for the perceptual and cognitive symptoms of schizophrenia. Emerging evidences suggest that interactions between different frequency bands, cross-frequency coupling (CFC), serve an important role in integrating sensory and cognitive information and may contribute to the pathophysiology of schizophrenia. Animal studies have utilized ketamine as a pharmacological model of disrupted neuronal oscillations, but few studies have examined its chronic effects on CFC. In the present study, we investigated the acute and chronic effects (14-day period) of ketamine (30 mg/kg i.p. each day) versus saline on alterations in the coupling of low-frequency (5-30 Hz) phase and high-frequency (30-100 Hz) amplitude in CA1 rat hippocampus. Intracranial electrode recordings were conducted daily pre and post-injection while the animals performed a foraging task on a four-arm rectangular maze. Physiological data were matched by locomotive speed across animal, condition and time point in order to control for variations in speed that may have obscured drug-related effects. Although acute effects of ketamine were observed on theta, slow gamma and fast gamma amplitude, these were all accompanied by significant differences in the saline group, obscuring the ability to detect drug-related acute effects. There were no chronic effects of ketamine on theta, slow gamma or fast gamma amplitude. Acute chronic effects were observed within the ketamine group but not the saline group across all frequency bands. Visual inspection of CFC plots confirmed two distinct ellipse-shaped patterns, the first of which occurred between 60-90 Hz amplitude (fast-gamma) and the second between 30-60 Hz amplitude (slow-gamma). Modeling differences in coupling patterns across time we found a chronic upward shift in the amplitude frequency location in the ketamine group but not the saline group post-injection. Our results demonstrate that chronic ketamine administration alters the interaction of low-frequency phase and high-frequency oscillations in the rat hippocampus. These findings provide evidence that CFC may serve as an important neuronal mechanism for cognitive and perceptual processes known to be impaired in schizophrenia.
Michaels, Timothy I., "Chronic Ketamine Alters Phase-Amplitude Cross-Frequency Coupling in the Rat Hippocampus: Implications for Translational Models of Schizophrenia Pathophysiology" (2017). Master's Theses. 1053.