학술논문

Effects of chronic ketamine on hippocampal cross‐frequency coupling: implications for schizophrenia pathophysiology.
Document Type
Article
Source
European Journal of Neuroscience. Oct2018, Vol. 48 Issue 8, p2903-2914. 12p. 4 Color Photographs, 3 Graphs.
Subject
*KETAMINE
*SCHIZOPHRENIA
*PATHOLOGICAL physiology
*HIPPOCAMPUS (Brain)
*METHYL aspartate antagonists
*LABORATORY rats
Language
ISSN
0953-816X
Abstract
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 disease pathophysiology. In this study, we investigated the effects of 14‐day consecutive administration of ketamine (30 mg/kg i.p.) vs. saline on alterations in amplitude and changes in the coupling of low‐frequency (0–30 Hz) phase and high‐frequency (30–115 Hz) amplitude in the CA1 hippocampus of Long Evans rats. Intracranial electrode recordings were conducted pre‐ and post‐injection while the animals performed a foraging task on a four‐arm rectangular maze. Permutation analysis of frequency band‐specific change in amplitudes revealed between‐group differences in theta (6–12 Hz) and slow gamma (25–50 Hz) but not fast gamma (65–100 Hz) bands at both slow and fast speeds. Chronic ketamine challenge resulted in decreased coupling (pre to post) at slow speeds but increased coupling at faster speeds, compared to either no or modest increased coupling in the saline group. These results demonstrate that chronic ketamine administration alters the interaction of low‐frequency phase and high‐frequency oscillations chronically and that such coupling varies as a function of locomotive speed. These findings provide evidence for the potential relevance of CFC to the pathophysiology of schizophrenia. We investigated the chronic effects of ketamine on oscillations in the CA1 hippocampus of Long Evans rats. There were between‐group differences in theta and slow gamma amplitude, but not fast gamma band amplitude. Ketamine decreased coupling (CFC) between low‐frequency phase and high‐frequency amplitude at slow speeds but increased coupling at faster speeds. These results suggest a potential role for CFC in the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]