Psilocybin Prolongs the Neurovascular Coupling Response in Mouse Visual Cortex
Rick Zirkel, Matthew Isaacson, Clara Liao, Ming Yi, Kenya Yamaguchi, Daniel Rivera, Amy Kuceyeski, Nozomi Nishimura, Alex C. Kwan, Chris B. Schaffer
bioRxiv (Cold Spring Harbor Laboratory) July 31, 2025 preprint DOI: 10.1101/2025.07.25.666803 via OpenAlex
Summary
AI-generated from the abstractPsilocybin prolongs increases in visual stimulus-evoked capillary blood flow in the mouse visual cortex without altering stimulus-evoked neural activity. This effect was reduced by pretreatment with a 5-HT2A receptor antagonist. Multi-modal widefield imaging confirmed extended vascular responses in surface vessels with no observed effect on population neural response. Computational simulations showed that prolonged neurovascular coupling responses can produce spurious increases in BOLD-based measures of functional connectivity. These findings demonstrate that psilocybin broadens neurovascular responses in the brain, highlighting the need to account for these effects when interpreting human neuroimaging data of psychedelic drug action.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Awake mice |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Neuroscience Visual cortex Neurovascular bundle Coupling piping |
| Citations | 3 |
| Key finding | Psilocybin prolongs stimulus-evoked capillary blood flow increases in the visual cortex without altering neural responses, an effect reduced by 5-HT2A receptor antagonism. |
Abstract
Abstract Psilocybin has profound therapeutic potential for various mental health disorders, but its mechanisms of action are unknown. Functional MRI studies have reported the effects of psilocybin on brain activity and connectivity; however, these measurements rely on neurovascular coupling to infer neural activity changes and assume that blood flow responses to neural activity are not altered by psilocybin. Using two-photon excited fluorescence imaging in the visual cortex of awake mice to simultaneously measure neural activity and capillary blood flow dynamics, we found that psilocybin administration prolonged the increase in visual stimulus-evoked capillary blood flow – an effect which was reduced by pretreatment with a 5-HT 2A R antagonist – despite not causing changes in the stimulus-evoked neural response. Multi-modal widefield imaging also showed that psilocybin extends the stimulus-evoked vascular responses in surface vessels with no observed effect on the population neural response. Computational simulation with a whole-brain neural mass model showed that prolonged neurovascular coupling responses can lead to spurious increases in BOLD-based measures of functional connectivity. Together, these findings demonstrate that psilocybin broadens neurovascular responses in the brain and highlights the importance of accounting for these effects when interpreting human neuroimaging data of psychedelic drug action.