The Nonclassic Psychedelic Ibogaine Disrupts Cognitive Maps.

Ibogaine, a psychedelic compound, destabilizes the cognitive map in the retrosplenial cortex of mice when they must infer their position between tactile landmarks. Using two-photon microscopy, researchers recorded neural activity in head-fixed mice running on a treadmill before and after ibogaine injection (40 mg/kg intraperitoneally). The drug increased neural activity rates, disrupted correlation structure, and heightened responses to cues, while leaving the size-frequency distribution of network activity events largely unchanged. These findings suggest that psychedelics disrupt representations that constrain neocortical activity, increasing neural signaling entropy. The loss of position encoding between landmarks resembles effects of hippocampal impairment, indicating that disruption of cognitive maps may contribute to discoordinated neocortical activity in psychedelic states.

Study at a glance

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.