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.
Psychedelic drugs such as psilocybin reduce the place specificity of neurons in the retrosplenial cortex of mice navigating a treadmill, making neural activity less tied to distinct locations. The stability of place-related activity across trials also decreases, and functional correlations among simultaneously recorded neurons are lowered. These effects are blocked by the serotonin 2A receptor antagonist ketanserin, indicating that the 5-HT2A receptor mediates them. The findings suggest that psychedelics increase the entropy of neural signaling, which may contribute to the disorientation often reported by humans after taking psychedelics.