Hippocampal phase precession is preserved under ketamine, but the range of precession across a theta cycle is reduced.

Abstract

Hippocampal phase precession, which depends on the precise spike timing of place cells relative to local theta oscillations, has been proposed to underlie sequential memory. N-methyl-D-asparate (NMDA) receptor antagonists such as ketamine disrupt memory and also reproduce several schizophrenia-like symptoms, including spatial memory impairments and disorganized cognition. It is possible that these impairments result from disruptions to phase precession. We used an ABA design to test whether an acute, subanesthetic dose (7.5 mg/kg) of ketamine disrupted phase precession in CA1 of male rats as they navigated around a rectangular track for a food reward. Ketamine did not affect the ability of CA1 place cells to precess despite changes to place cell firing rates, local field potential properties and locomotor speed. However, ketamine reduced the range of phase precession that occurred across a theta cycle. Phase precession is largely robust to acute NMDA receptor antagonism by ketamine, but the reduced range of precession could have important implications for learning and memory.