Cell-type specific transcriptional modulation by psilocybin induces sustained plasticity in mouse medial prefrontal cortex
Delong Zhou, Heike Schuler, Vedrana Cvetkovska, Juliet Meccia, Ashot S. Harutyunyan, Jiannis Ragoussis, Rosemary C. Bagot, Ashot S. Harutyunyan, Jiannis Ragoussis, Danilo Bzdok, Rosemary C. Bagot
bioRxiv (Cold Spring Harbor Laboratory) January 8, 2025 preprint DOI: 10.1101/2025.01.08.631940 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Intervention | Psilocybin |
| Dose | single dose |
| Duration | 24 hours post-psilocybin |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Prefrontal cortex Cell type |
| Citations | 2 |
| Key findings | Psilocybin's sustained neuroplastic effects in the mouse medial prefrontal cortex are mediated by 5-HT 2C signaling and L5/6 NP neurons. |
Abstract
Abstract Despite enormous interest in psychedelics for psychiatric interventions, potential underlying biological mechanisms remain unclear. Here, we confirm that a single dose of psilocybin increases synaptic transmission in mouse medial prefrontal cortex. Using scRNA-sequencing, we identify cell-type specific mechanisms of sustained neuroplastic effects. We show that, 24h post-psilocybin, expression of plasticity-related genes is increased in excitatory neurons and that transcription in a type of deep layer near projecting neuron, L5/6 NP, is robustly altered. Analyzing receptor expression patterns reveals that this cell-type specificity does not align with 5-HT 2A expression but aligns with 5-HT 2C expression patterns. Further, multivariate analyses identify psilocybin-induced gene expression patterns in L5/6 NP neurons predict 5-HT 2C , but not 5-HT 2A , transcript levels. Pharmacologic manipulation with a 5-HT 2C antagonist attenuates the post-acute sustained effect of psilocybin on synaptic transmission, highlighting 5-HT 2C signaling and L5/6 NP neurons as key mediators of psychedelic drug action’s sustained neuroplastic effects in mPFC.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 2
Cites 32
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
and 27 more in the library