bioRxiv : the preprint server for biologyAug 1, 2026

Psychedelic drugs affect nerve cell branches differently depending on behavior and serotonin receptors

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

Psilocybin transiently increases calcium event rates in dendritic tufts of mouse pyramidal tract neurons during quiet wakefulness.

The drug's effect on calcium dynamics aligns with its pharmacokinetics in the brain.
Calcium event rates increase selectively during periods of quiet wakefulness.
The increase in calcium signaling is abolished when the 5-HT2A receptor is deleted.
Under normal conditions, dendritic calcium signaling can predict spine formation, but this is disrupted by psilocybin.
The findings indicate that psilocybin alters the connection between immediate dendritic activity and long-term structural changes.

Simplified

How psychedelics act on cortical dendrites to produce long-lasting structural plasticity remains poorly understood. Here, we characterize the effects of psilocybin on dendritic calcium dynamics in pyramidal tract neurons of the mouse medial frontal cortex. Psilocybin transiently increases calcium event rates in apical dendritic tufts over a time course that parallels the drug's pharmacokinetics in the brain. This acute effect is brain state-dependent, occurring selectively during quiet wakefulness, and was abolished by cell type-specific deletion of the 5-HT _2A receptor. Under control conditions, dendritic calcium signaling predicts subsequent spine formation, but this relationship is not preserved following psilocybin administration. Together, these findings reveal that psilocybin engages brain state- and 5-HT _2A receptor-dependent dendritic signaling, while altering the relationship between acute dendritic activity and long-term structural plasticity. The results suggest that the mechanisms linking acute dendritic signaling to structural remodeling differ between physiological and psychedelic-induced plasticity.