Increased inhibitory input to CA1 pyramidal cells alters hippocampal gamma frequency oscillations in the MK-801 model of acute psychosis

Abstract

The phencyclidine compound MK-801 can induce psychosis with symptoms which closely resemble those observed in an acute schizophrenic episode. Here we used an in vitro model of psychosis after systemic administration of MK-801. We found that kainate-induced gamma frequency field oscillations in animals previously exposed to MK-801 have significantly higher power than in control animals. The intrinsic membrane properties of pyramidal cells, such as membrane input resistance and time constant, were not found to be different. In contrast, the MK-801 cells exhibited significantly more depolarized resting membrane potentials than control cells. We propose cellular alterations in Na+-K+-pump activity and increases in phasic inhibition in MK-801 cells to be the respective underlying mechanisms responsible for the more depolarized resting membrane potentials and the increased power of gamma frequency oscillations observed in MK-801 pretreated animals.

Keywords

• Schizophrenia
• Network oscillations
• MK-801
• Hippocampus
• IPSPs
• Na+-K+-pump