Mapping excitatory synaptic plasticity evoked by single-dose psilocybin in mice
Ziming Li, Crystal Weber, Francesca Sellitti, Linda D. Simmler
Study at a glance
AI-extracted from the abstract| Characteristics | Basic science study |
|---|---|
| Population | Mice |
| Intervention | Psilocybin |
| Duration | 24 hours after treatment |
| Topics | Neuroplasticity Psilocybin |
| Key points | Psilocybin selectively increased the frequency of miniature excitatory postsynaptic currents in specific cortical subregions and the amygdala 24 hours after a single dose, and this effect was prevented by post-synaptic Htr2a knockout in the insular/orbitofrontal cortex, demonstrating region-specific, 5-HT2A receptor-dependent excitatory synaptic plasticity. |
Abstract
Abstract A single dose of psilocybin can induce long-lasting antidepressant effects. The neurobiological mechanisms underlying such sustained antidepressant effect remain insufficiently understood, particularly at the level of synaptic function and drug-target specificity. Here, we aimed to delineate single-dose psilocybin-induced excitatory synaptic plasticity. Synaptic plasticity was assessed by whole-cell patch-clamp recording of excitatory synaptic transmission 24 h after treating mice with single-dose psilocybin. We correlated the recordings with transcriptomics data and used a conditional single-vector CRISPR/SaCas9-dependent knock-out strategy to validate the role of the 5-HT 2A receptor. Psilocybin selectively increased the frequency of miniature excitatory postsynaptic currents in specific cortical sub-regions and in the amygdala. Frequency correlated with the expression levels of psilocin-targeted serotonin receptors, when expression heterogeneity between cortical subregions and along the anterior-posterior axis was accounted for. Post-synaptic Htr2a knock-out in the insular/orbitofrontal cortex precluded psilocybin-induced 24-h plasticity. These findings demonstrate that lasting psilocybin-induced effects on excitatory synaptic transmission manifest with brain-region specificity, likely reflecting a functional consequence of synapse formation. This work establishes a foundation for a circuit-specific, mechanistic understanding of functional aspects of psilocybin-induced neuroplasticity.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cites 30
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
and 25 more in the library