Psilocybin’s Brain-Wide Rewiring Mapped with Novel Viral Tracing Technique
Researchers have gained unprecedented insight into how psilocybin alters brain circuitry, revealing a widespread rewiring affect previously suspected but difficult to pinpoint. A study led by Yale’s Kwan lab utilized a unique combination of psilocybin management and rabies virus tracing to map the specific neural connections impacted by the psychedelic compound.
Previous research established that psilocybin induces long-lasting changes in the brain, prompting the question of where these changes occur.To address this, the team moved beyond customary optical imaging of synapses and employed a modified rabies virus developed by collaborators at the allen Institute for Brain Science. This virus, engineered to travel between neurons, effectively “charts the brain’s wiring diagram” by labeling connected neurons with fluorescent proteins.
The experiment involved administering a single dose of psilocybin to mice, followed a day later by the rabies virus.after a week of incubation, brain imaging revealed significant alterations in connectivity compared to control mice.
Specifically, the study found that psilocybin weakened recurrent connections within the cortex - the brain’s feedback loops. Researchers believe this is notably relevant to depression, as these loops can contribute to rumination and persistent negative thought patterns. By reducing these feedback loops,the findings support the idea that psilocybin may disrupt this cycle.
Furthermore, the research demonstrated increased connectivity between the sensory area of the brain and subcortical regions, strengthening the link between perception and action.
Surprisingly, the rewiring effect wasn’t limited to a few brain regions. Kwan noted the changes were “brain-wide,” a scale of impact not previously observed in similar studies. The team also discovered that the level of neural activity within a region influences how psilocybin rewires the circuitry. By manipulating neural activity, they were able to demonstrably alter the drug’s effects on brain connections.
This revelation opens avenues for therapeutic development, potentially allowing researchers to selectively enhance beneficial plasticity while mitigating negative changes induced by psilocybin.The research was supported by One Mind and the National Institutes of Health and involved contributions from researchers at Yale University, the Allen Institute for Brain Science, University of California, Irvine, and the Chinese University of Hong Kong.
