Nature
June 1, 2025
Ling-Xiao Shao, Clara Liao, Pasha A Davoudian et al.
75 citations
A single dose of psilocybin increases dendritic spine density in two types of pyramidal cells in the mouse medial frontal cortex: subcortical-projecting pyramidal tract (PT) and intratelencephalic (IT) neurons. Silencing PT neurons eliminates psilocybin's ability to reduce stress-related behaviors, while silencing IT neurons has no effect. Psilocybin boosts synaptic calcium transients and firing rates specifically in PT neurons shortly after administration. Knocking out the 5-HT2A receptor blocks psilocybin's effects on both stress-related behavior and structural plasticity. These findings identify PT neurons and the 5-HT2A receptor as essential for psilocybin's long-term actions.
Nature reviews. Neuroscience
February 1, 2025
Clara Liao, Alisha N Dua, Cassandra Wojtasiewicz et al.
60 citations
A feature of major depressive disorder is impaired excitatory synapses in the prefrontal cortex. Treatments with rapid antidepressant effects—ketamine, electroconvulsive therapy, and non-invasive neurostimulation—appear to enhance neural plasticity, but the specific forms and mechanisms linking these interventions to restoring excitatory synaptic function remain unknown. This review highlights preclinical research from the past 15 years showing that ketamine and psychedelic drugs can trigger growth of dendritic spines in cortical pyramidal neurons.
Nature Communications
February 12, 2025
Farid Aboharb, Pasha A. Davoudian, Ling-Xiao Shao et al.
19 citations
A machine-learning pipeline using light sheet fluorescence microscopy to measure immediate early gene expression in mouse brain tissues classified psychoactive drugs with 67% accuracy across eight conditions, significantly above the 12.5% chance level. Psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with over 95% accuracy. Shapley additive explanation identified brain regions driving predictions, suggesting a novel approach for characterizing and validating psychoactive drugs with psychedelic properties.
bioRxiv : the preprint server for biology
November 23, 2024
Farid Aboharb, Pasha A Davoudian, Ling-Xiao Shao et al.
3 citations
preprint
A pipeline using light sheet fluorescence microscopy to measure immediate early gene expression in mouse brain tissues, combined with machine learning, can classify psychoactive drugs including psilocybin, ketamine, and MDMA. In one-versus-rest tests, the exact drug was identified with 67% accuracy, far above the 12.5% chance level. Psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with over 95% accuracy in pairwise comparisons. Shapley additive explanation identified brain regions driving the predictions. The approach offers a novel way to characterize and validate psychedelic and related compounds.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2024
Ling-Xiao Shao, Clara Liao, Pasha A Davoudian et al.
preprint
A single dose of psilocybin increased the density of dendritic spines in both subcortical-projecting pyramidal tract (PT) and intratelencephalic (IT) cell types in the mouse medial frontal cortex. Silencing PT neurons eliminated psilocybin's ability to ameliorate stress-related phenotypes, whereas silencing IT neurons had no detectable effect. In PT neurons only, psilocybin boosted synaptic calcium transients and elevated firing rates acutely after administration. Targeted knockout of 5-HT2A receptors abolished psilocybin's effects on stress-related behavior and structural plasticity. These results identify a pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex as essential for psilocybin's long-term drug action.