Ketamine evoked disruption of entorhinal and hippocampal spatial maps

Francis Kei Masuda, Emily A. Aery Jones, Yanjun Sun and Lisa M. Giocomo ()
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Francis Kei Masuda: Stanford University School of Medicine
Emily A. Aery Jones: Stanford University School of Medicine
Yanjun Sun: Stanford University School of Medicine
Lisa M. Giocomo: Stanford University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine’s impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal’s spatial position, as mice navigated virtual reality and real world environments. Ketamine acutely increased firing rates, degraded cell-pair temporal firing-rate relationships, and altered oscillations, leading to longer-term remapping of spatial representations. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings demonstrate ketamine-induced dysfunction of the MEC-hippocampal circuit at the single cell, local-circuit population, and network levels, connecting previously demonstrated physiological effects of ketamine on spatial cognition to alterations in the spatial navigation circuit.

Date: 2023
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DOI: 10.1038/s41467-023-41750-4

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