Hippocampal sharp wave ripple events and place cell activity in a ketamine model of schizophrenia

Abstract

This experiment aimed to explore the role of hippocampal activity in a pharmacological model of schizophrenia, focusing on hippocampal place cell firing and associated sharp wave ripple events. In a within-subjects design, rats with tetrodes implanted in area CA1 of the hippocampus were administered either saline or a subanesthetic dose of ketamine across separate, three day sequences. Following injection, single cell and local field potential activity were recorded while the animals ran laps of a rectangular track for a reward, and again while they sat in a rest box. All animals completed both control and experimental sequences. In the control sequences, saline was administered on each of three consecutive days, while in the experimental sequences, the drug and control trials were alternated across consecutive days. Specifically, saline was administered on day one, ketamine on day two, and saline on day three. Results demonstrated that in both rest and run conditions, ketamine reduced the intrinsic frequency of sharp wave ripples, but did not alter any other ripple measures. None of the single cell measures were affected by ketamine administration in the rest nor run condition. Taken together, the results suggested that decreased sharp wave ripple frequency in the hippocampus may produce some of the schizophrenia-like symptoms observed in the ketamine model, but that the activity of individual place cells is not affected. The findings further support the glutamate theory of schizophrenia, as well as the role of the hippocampus in producing symptoms of the disorder.