Ketamine disrupts theta synchrony across the septotemporal axis of the CA1 region of hippocampus.

The hippocampal theta signal reflects moment-to-moment variation in the synchrony of synaptic input to hippocampal neurons. Consistent with the topography of hippocampal afferents, the synchrony (coherence) of the theta signal varies across the septotemporal axis. Septotemporal variation in the theta signal can also be observed in relation to ongoing and past experience. Thus there is a systematic decrease in the relationship between locomotor speed and theta power across the septotemporal axis, septal hippocampus exhibiting the strongest relationship. Conversely, theta in temporal hippocampus decrements over repeated behavioral experience (running episodes), while theta in the septal hippocampus does not. Ketamine is an N-methyl-D-aspartate (NMDA) antagonist that can decrease theta power. The present study examined whether ketamine treatment could alter theta coherence across the long axis independent of changes in locomotor behavior. Rats were well trained to navigate a linear runway and outfitted with electrodes at different septotemporal positions within CA1. Locomotor behavior and theta coherence and power were examined after administration of 2.5 and 10 mg/kg ketamine. Ketamine (2.5 mg/kg) decreased theta coherence between distant CA1 electrode sites without altering running speed or theta power. Both doses of ketamine also blunted and reversed the decrement in theta power observed at midseptotemporal and temporal electrodes over repeated run sessions. The results demonstrate the sensitivity of global network synchronization to relatively low doses of ketamine and septotemporal differences in the influence of ketamine on hippocampal dynamics in relation to past experience.