The Nonclassic Psychedelic Ibogaine Disrupts Cognitive Maps

Area of Science:

• Neuroscience
• Psychopharmacology
• Cellular Biology

Background:

• Psychedelic compounds are known to alter mental function, but their effects on cellular information encoding are not well understood.
• Investigating the neural mechanisms underlying psychedelic experiences is crucial for understanding their impact on cognition.

Purpose of the Study:

• To investigate the effects of the nonclassic psychedelic ibogaine on neural activity and cognitive map stability in the retrosplenial cortex.
• To explore how ibogaine influences neuronal ensemble representations of spatial information.

Main Methods:

• Two-photon microscopy was used to record neural activity in the retrosplenial cortex of head-fixed mice.
• Mice ran on a treadmill before and after intraperitoneal injection of ibogaine (40 mg/kg).

Main Results:

• Ibogaine destabilized the cognitive map, impairing the representation of position between tactile landmarks.
• Neural activity showed increased rates, loss of correlation structure, and heightened cue responses after ibogaine administration.
• Network activity event size and frequency remained largely unaffected, indicating preserved signal propagation.

Conclusions:

• Psychedelic compounds like ibogaine may disrupt neocortical representations, increasing neural signaling entropy.
• The observed disruption of cognitive maps by ibogaine mirrors effects of hippocampal impairment, suggesting a potential mechanism for psychedelic-induced discoordination.