Investigation of CA1 and DG delta oscillations in response to systemic administration of the NMDAr antagonist ketamine

Abstract

Brain oscillatory activity generated by populations of neurons has provided advances in our understanding of brain function in normal and pathological conditions. Recent reports have used systemic administration of the NMDA receptor antagonist ketamine as an animal model to study schizophrenia. These studies revealed the disturbance of normal oscillatory activity in many brain areas like the thalamus, prefrontal cortex, and in the hippocampus. For instance, the amplitude of low-frequency oscillations in the delta band (1-4 Hz) increases in the hippocampus. However, it is still unclear whether specific subareas of the hippocampus are equally affected. Our aim was to investigate the amplitude modulation of delta oscillation in CA1 and Dentate Gyrus (DG) of the rat hippocampus in response to the systemic administration of saline and three sub anesthetic doses of ketamine (25 mg/kg, 50 mg/kg e 75 mg/kg). We found that the CA1 and DG delta oscillations are modulated by NMDAr antagonist ketamine in a dose-dependent manner. Specifically, ketamine at doses of 50 mg/kg and 75 mg/kg significantly increased the amplitude of delta oscillations both in CA1 and DG when compared to saline. In addition, when we analyzed intervals that animals presented locomotion speed lower than 5 cm/s, we found that ketamine at doses of 50 mg/kg and 75 mg/kg significantly increased delta amplitude in CA1, but not DG. These results suggest that hippocampal delta oscillations are modulated in CA1 and DG under effect on NMDA antagonist ketamine.