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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
August 1, 2023
Sarah J Jefferson, Ian Gregg, Mark Dibbs et al.
57 citations
5-MeO-DMT, a short-acting psychedelic, produces a dose-dependent increase in head-twitch response in mice that is shorter in duration than psilocybin at all doses tested. It also substantially suppresses social ultrasonic vocalizations during mating behavior. The compound causes long-lasting increases in dendritic spine density in the mouse medial frontal cortex, driven by an elevated rate of spine formation, but unlike psilocybin, it does not affect the size of dendritic spines. These findings reveal behavioral and neural mechanisms of 5-MeO-DMT, highlighting similarities and differences with psilocybin.
ACS Chemical Neuroscience
August 1, 2024
Samuel C Woodburn, Caleb M Levitt, Allison M Koester et al.
28 citations
Psilocybin robustly enhances fear extinction in male and female mice when given acutely before testing, across all doses tested. It also produces long-term improvements in extinction retention and reduces fear renewal in a novel context, though these effects depend on dose. Females may respond to a narrower dose range than males. Administration before fear learning or immediately after extinction does not alter behavior, showing that concurrent extinction experience is necessary. Blocking the 5-HT2A receptor eliminates psilocybin's effects on extinction, retention, and renewal, while blocking the 5-HT1A receptor only attenuates the effect on fear renewal. These findings highlight dose, context, and serotonin receptors as key factors in psilocybin's facilitation of fear extinction.
Brain, behavior, and immunity
July 2, 2026
Samuel C Woodburn, Alexander M Kuhn, Kelly E Bosis et al.
Ketamine promotes spine growth on the apical dendrites of pyramidal neurons in the prefrontal cortex (PFC), and brain-derived neurotrophic factor (BDNF) signaling is critical for these effects. In mice, ketamine (10 mg/kg) reduced immobility in the forced swim test and increased dendritic spine density on PFC pyramidal neurons. These effects were associated with reduced microglia ramification and increased Bdnf expression in sorted PFC microglia. Mice with microglial Bdnf depletion (Cx3cr1Cre/+:Bdnffl/fl) showed decreased GluN2B levels in PFC synaptosomes, attenuated behavioral responses, and no change in dendritic spine density after ketamine. The results implicate microglia in the neurobiological and behavioral effects of ketamine.
bioRxiv : the preprint server for biology
April 22, 2026
Cory A Knox, Samuel C Woodburn, Amelia D Gilbert et al.
Psilocybin, a classic psychedelic, increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress in mice, demonstrating its effects in a translationally relevant animal model. Prior studies had largely examined stress-naive animals, so these findings show that psilocybin can promote neural plasticity and behavioral recovery even after chronic stress.
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.