Psilocybin Triggers Activity-Dependent Rewiring of Large-Scale Cortical Networks

Quan Jiang and colleagues, led by Alex Kwan, with researchers from Cornell University, the Allen Institute for Brain Science, UC Irvine, and collaborating institutions

This study, published in Cell, examines a more basic question: when psilocybin causes new neural connections to form, what determines which connections actually change?

The researchers used a modified rabies virus as a tracing tool. The virus lets them label neurons that provide input to particular cells, so they can map where those connections come from before comparing psilocybin-treated animals with controls. This is a laboratory tracing method and has nothing to do with studying rabies infection.

The changes in connectivity were selective. Pathways carrying information from perceptual and medial cortical regions toward subcortical targets became stronger, while portions of recurrent communication within the cortex became weaker.

The researchers then manipulated activity in one of those input regions. When they suppressed that activity during psilocybin exposure, the later pattern of rewiring changed. Neural activity during psilocybin exposure helped determine which connections were subsequently strengthened.

Plasticity means that the nervous system has an increased capacity to change. It does not mean that every change will be useful. If the circuits active during that period influence which connections become stronger or weaker, then what the nervous system does during the plastic period may help determine where the change goes.

This gives me a biological mechanism to examine within Neural Attunement: whether activity during plasticity shapes later changes. Whether psychotherapy, coaching, environmental cues, or integration produce comparable effects in humans remains untested by this mouse study.

The next logical experiment is to deliberately activate a defined functional system during a period of psychedelic-induced plasticity and then measure what happens to that system afterward. Reward learning, threat extinction, interoception, cognitive control, salience, and social learning are all candidates.