Ketamine evoked disruption of entorhinal and hippocampal spatial maps
bioRxiv Preprint Server – February 05, 2023
Source: bioRxiv
Summary
Ever wonder why ketamine can cause out-of-body sensations? New research sheds light on how this antidepressant impacts the brain's internal GPS. Using advanced imaging in mice, scientists found ketamine acutely disrupted spatial maps in the entorhinal cortex, boosting neuron activity. Concurrently, activity in the hippocampus, vital for position sense, was suppressed. These precise findings pinpoint a neural circuit disruption as the basis for ketamine's spatial effects.
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 induced an acute disruption and long-term re-organization of entorhinal spatial representations. This acute ketamine-induced disruption reflected increased excitatory neuron firing rates and degradation of cell-pair temporal firing rate relationships. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings point to disruption in the spatial coding properties of the entorhinal-hippocampal circuit as a potential neural substrate for ketamine-induced changes in spatial cognition.