# Cellular basis of psilocybin actions in frontal cortex

> **NIH NIH R01** · CORNELL UNIVERSITY · 2022 · $598,277

## Abstract

PROJECT SUMMARY
 Psychedelics are compounds that produce an atypical state of consciousness characterized by altered
perception, cognition, and mood. Among psychedelics, psilocybin has gained attention recently because early
clinical trials indicated potential antidepressant effects, leading to a ‘breakthrough therapy’ designation from the
FDA to test psilocybin for major depressive disorder. However, despite the promise, the biological mechanisms
underpinning psilocybin’s potential therapeutic action are poorly understood. Our lab employs subcellular-
resolution two-photon microscopy to visualize dendritic structure and function in head-fixed mice. The goal of
this project is to characterize how a single dose of psilocybin may alter dendritic architecture in the medial
frontal cortex of the mouse and the associated cellular mechanisms. The hypothesis is that psilocybin
promotes spine formation by activating specific serotonin receptor subtypes and exerts differential effects on
distinct subtypes of pyramidal neurons. To test the hypothesis, we propose a series of experiments that
combine subcellular-resolution optical imaging, conditional knockouts, and causal perturbations in mice. The
results will answer crucial questions regarding psilocybin’s ability to promote structural plasticity in vivo and
delineate receptors and cellular factors that underlie the plasticity-promoting actions. We expect the
mechanistic insights will be important as the field evaluates psychedelics as a potential treatment option for
neuropsychiatric disorders and searches for novel antidepressants.

## Key facts

- **NIH application ID:** 10516272
- **Project number:** 1R01MH128217-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** CHUN-HAY ALEX KWAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $598,277
- **Award type:** 1
- **Project period:** 2022-08-19 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10516272

## Citation

> US National Institutes of Health, RePORTER application 10516272, Cellular basis of psilocybin actions in frontal cortex (1R01MH128217-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10516272. Licensed CC0.

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