Researchers used genetically engineered, nonpathogenic rabies virus tracers to produce a brain‑wide map of how psilocybin affects neural circuits in mice. The team found that psilocybin may weaken cortical feedback loops linked to negative, self‑referential thinking while boosting connectivity in circuits that convert sensory inputs into action. The study — led by groups in China, Hong Kong, and the U.S. — appears in Cell, but authors caution that viral tracers can spread non‑synaptically and mouse brains differ from humans.
Engineered Rabies Virus Reveals How Psilocybin Rewires the Brain
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Psychedelic mushrooms and their active ingredient, psilocybin, have sparked renewed scientific interest for their rapid and sometimes dramatic effects on brain organization and mood. Although clinical studies suggest psilocybin can help treat depression, the detailed neural mechanisms behind its mind‑altering effects remain incompletely understood.
To address that gap, an international team of researchers from China, Hong Kong, and the United States adapted harmless, genetically modified rabies viruses as neural tracers to map psilocybin’s influence across the mouse brain. By combining psilocybin with two viral tracers—one being a rabies virus engineered to infect only selected neurons and spread along chosen synaptic connections—the scientists generated a brain‑wide map of circuit changes after psilocybin exposure.
Key Findings
The study found two notable effects in mice: psilocybin appeared to weaken certain cortical feedback loops that are thought to sustain negative, self‑referential patterns of thinking, while simultaneously increasing connectivity in circuits that translate sensory input into actions. Using the rabies tracer’s natural ability to traverse synapses, the team observed neuronal changes consistent with increased synapse formation in affected pathways.
“This is really looking at brain‑wide changes,” said Cornell University biomedical engineer and coauthor Alex Kwan. “That’s a scale that we have not worked at before. A lot of times, we’re focusing on a small part of the neural circuit.”
Methods and Caveats
Methodologically, the researchers chemically paired psilocybin with two viral tracers to follow how the compound’s influence propagated across circuits. The engineered rabies virus was chosen for its ability to move across neuronal synapses, but the authors emphasize important caveats: modified rabies tracers can sometimes reach nearby cells via non‑synaptic routes, potentially confounding circuit maps, and mouse brains differ substantially from human brains, limiting direct clinical extrapolation.
Implications
Despite these limitations, the work provides valuable, brain‑wide clues about how psilocybin reorganizes neural networks and suggests mechanisms—such as weakening maladaptive cortical feedback and strengthening sensory‑to‑action pathways—that could underlie its therapeutic effects. The authors note that further studies in higher‑order models and humans are needed to evaluate clinical relevance.
The study was published in the journal Cell.
