Ketamine evoked disruption of entorhinal and hippocampal spatial maps
Francis Kei Masuda, Yanjun Sun, Emily A Aery Jones, Lisa M Giocomo
bioRxiv Preprint Server February 5, 2023 preprint DOI: 10.1101/2023.02.05.527227 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Antidepressant Dissociative Brain research Neural mechanisms Neurobiology Spatial cognition Spatial awareness Navigation Internal gps Position sense Out-of-body experience Brain circuits Entorhinal cortex Hippocampus Neural pathways |
| Citations | 2 |
| Key findings | Ketamine acutely disrupts and then re-organizes spatial representations in the entorhinal cortex while suppressing hippocampal position-encoding neurons, pointing to entorhinal-hippocampal circuit disruption as a neural substrate for ketamine-induced spatial cognition changes. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 8
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Deep posteromedial cortical rhythm in dissociation Nature September 16, 2020
- Anomalous bodily-self experiences among recreational ketamine users. Cognitive Neuropsychiatry 2012
- Impaired Spatial Memory after Ketamine Administration in Chronic Low Doses Current Neuropharmacology March 1, 2011
and 3 more in the library