Ketamine evoked disruption of entorhinal and hippocampal spatial maps

• Published in: Nature communications Vol. 14; no. 1; pp. 6285 - 19
• Main Authors: Masuda, Francis Kei, Aery Jones, Emily A., Sun, Yanjun, Giocomo, Lisa M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/2649; 631/378/3920; 64; 64/60; 9/30; Animals; Antidepressants; Calcium imaging; Circuits; Cognition; Cognition & reasoning; Computer applications; Cortex (entorhinal); Electrophysiology; Entorhinal Cortex - physiology; Hippocampus; Hippocampus - physiology; Humanities and Social Sciences; Ketamine; Ketamine - adverse effects; Memory tasks; Mice; multidisciplinary; Navigation; Navigation behavior; Neural coding; Neuroimaging; Neurons; Neurons - physiology; Physiological effects; Science; Science (multidisciplinary); Side effects; Spatial analysis; Spatial discrimination; Spatial memory; Substrates; Temporal lobe; Virtual reality
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41750-4

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. Ketamine’s antidepressant effects can be accompanied by altered spatial cognition. Here, the authors record from thousands of neurons in awake behaving mice to reveal how ketamine disrupts coding in the spatial navigation circuit.