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Neil K. Savalia

Cornell University

6 papers in the library · 743 citations · publishing 2020-2025

Papers

Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

bioRxiv (Cold Spring Harbor Laboratory) February 17, 2021 Ling-Xiao Shao, Clara Liao, Ian Gregg et al. 26 citations preprint

A single dose of psilocybin, a serotonergic psychedelic, caused a roughly 10% increase in the size and density of dendritic spines on layer 5 pyramidal neurons in the mouse medial frontal cortex. This structural remodeling began within 24 hours and persisted for at least one month, driven by an elevated rate of new spine formation. The drug also reduced stress-related behavioral deficits and increased excitatory neurotransmission. The findings demonstrate that psilocybin induces fast and enduring synaptic rewiring in the cortex, which may provide a structural basis for long-term integration of experiences and lasting therapeutic benefits.

DOI: 10.1101/2021.02.17.431629 Full text Psilocybin Serotonergic Serotonin Dendritic spine +12

Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks

Cell December 5, 2025 Quan Jiang, Ling-Xiao Shao, Shenqin Yao et al. 15 citations

A single dose of psilocybin causes structural remodeling of dendritic spines in the medial frontal cortex of mice. Using monosynaptic rabies tracing, the researchers mapped brain-wide inputs to frontal cortical pyramidal neurons and found that psilocybin's effect on connectivity is network specific: it strengthens routing of inputs from perceptual and medial regions (homolog of the default mode network) to subcortical targets while weakening inputs that are part of cortico-cortical recurrent loops. The pattern of synaptic reorganization depends on drug-evoked spiking activity, as silencing a presynaptic region during psilocybin administration disrupts the rewiring. These results reveal how psilocybin impacts large-scale cortical network connectivity and show that neural activity modulation can sculpt psychedelic-evoked plasticity.

DOI: 10.1016/j.cell.2025.11.009 Psilocybin Neuroplasticity Default mode network Dendritic spine +11

Single-nucleus transcriptomics reveals time-dependent and cell-type-specific effects of psilocybin on gene expression

bioRxiv (Cold Spring Harbor Laboratory) January 4, 2025 Clara Liao, Ethan O'Farrell, Yaman Qalieh et al. 3 citations preprint

A single dose of psilocybin triggers time-dependent and cell-type-specific changes in gene expression in the medial frontal cortex of mice. Excitatory neurons showed altered genes involved in synaptic plasticity, while GABAergic neurons showed changes in genes related to mitochondrial function and metabolism. These transcriptional responses occurred in an early phase at 1-2 hours and a late phase at 72 hours after administration. Ketamine produced similar transcriptional changes. These findings suggest that psilocybin's long-term neural and behavioral effects may stem from lasting alterations in gene expression.

DOI: 10.1101/2025.01.04.631335 Psilocybin Gabaergic Neuroscience Biology +4

Visualizing drug actions on dendrites: psilocybin and other classic psychedelics

January 1, 2023 Ling-Xiao Shao, Clara Liao, Ian Gregg et al.

Psychedelics like psilocybin can alter neuronal structure in the frontal cortex. Using two-photon microscopy in mice, psilocybin administration led to changes in dendritic spines, the tiny protrusions on neurons that receive signals from other neurons. The effects were compared with those of other psychoactive drugs, suggesting that psychedelics may have unique impacts on brain cell architecture. These findings indicate a potential mechanism for how psychedelics could influence brain function and behavior.

DOI: 10.1364/brain.2023.btu2b.2 Psilocybin Hallucinogen Neuroscience Cortex anatomy +4