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Single Psilocybin Dose Rewires Brain-Wide Circuits in Mice, Cell Study Finds

A rabies-based tracer mapped reduced cortical feedback alongside stronger sensory-to-subcortical links in a preclinical model relevant to depression.

Overview

  • The Cornell-led collaboration reported the results Dec. 5 in Cell, with Quan Jiang as lead author and Alex Kwan as senior author.
  • Connectivity mapping showed weakened recurrent cortico-cortical loops often associated with rumination in depression.
  • The drug increased connections from sensory cortex to subcortical regions, reinforcing perception–action pathways.
  • Researchers delivered one psilocybin dose, introduced a synapse-hopping rabies virus a day later, then imaged brains a week later to compare with controls.
  • Rewiring depended on neural firing levels, and experimentally shifting activity redirected which circuits changed, suggesting manipulable plasticity that remains to be validated in humans; the work was funded by the NIH and One Mind.