The Nonclassic Psychedelic Ibogaine Disrupts Cognitive Maps.
Biological psychiatry global open science – January 01, 2024
Source: PubMed
Summary
A fascinating insight reveals how psychedelics alter our internal navigation. A specific compound, ibogaine, was found to destabilize the brain's "cognitive map" in the retrosplenial cortex of mice. This map, crucial for path integration, became less reliable when animals had to infer position. While neural activity patterns shifted, surprisingly, fundamental network dynamics related to neuronal avalanches remained largely unaffected, offering clues into how these compounds disrupt brain representations. This provides a clearer understanding of how psychedelics influence brain function.
Abstract
The ability of psychedelic compounds to profoundly alter mental function has been long known, but the underlying changes in cellular-level information encoding remain poorly understood. We used two-photon microscopy to record from the retrosplenial cortex in head-fixed mice running on a treadmill before and after injection of the nonclassic psychedelic ibogaine (40 mg/kg intraperitoneally). We found that the cognitive map, formed by the representation of position encoded by ensembles of individual neurons in the retrosplenial cortex, was destabilized by ibogaine when mice had to infer position between tactile landmarks. This corresponded with increased neural activity rates, loss of correlation structure, and increased responses to cues. Ibogaine had surprisingly little effect on the size-frequency distribution of network activity events, suggesting that signal propagation within the retrosplenial cortex was largely unaffected. Taken together, these data support proposals that compounds with psychedelic properties disrupt representations that are important for constraining neocortical activity, thereby increasing the entropy of neural signaling. Furthermore, the loss of expected position encoding between landmarks recapitulated effects of hippocampal impairment, suggesting that disruption of cognitive maps or other hippocampal processing may be a contributing mechanism of discoordinated neocortical activity in psychedelic states.