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The study maps how psilocybin restores brain circuits linked to depression

An international collaboration led by Cornell researchers used a combination of psilocybin and rabies virus to map how and where the psychedelic compound rewires connections in the brain.

In particular, psilocinBin appears to destroy the cortical cortex that can lock people into negative thinking.Psilocybin also strengthens the pathway to the subcortical area that stops the perception of beauty on access, basically the motor response.

Expect to be released on December 5th in the cell.Lead author is Quan Simpdoctoral Research Paper.

The project is the latest step in discoveries made by Alex Kwan, Ph.D.'09, a professor of biomedical engineering at Cornell engineering and senior author of the paper.Kwan's lab is passionate about developing therapeutic treatments for depression, such as psilocybin, Ketamine, and 5 Meo-DMT, which repair the brain's neurological circuitry.

Psilocybin, the active ingredient in psychedelic mushrooms, is a promising candidate for drug development because clinical trials have shown that the psychedelic drug can reduce symptoms in depressed people for weeks or even months after a single treatment.

In 2021, Guan's team used a high-resolution optocybin treatment to show the ability to structure - by improving its structure - by growing its cartilage.

Exploring how psilocybin rewires circuits

"Many people were happy with the previous study, because psychedelics promised treatment, but we didn't know why they worked. Our study showed that it takes a long time to get back into the brain," Kahn said."One of the key questions was that, although we show that new connections are made, we don't know where they connect. Are there parts of this study that have been rediscovered?"

To achieve this, Kwan's group took a novel approach.Instead of using optics to image individual synaptic connections, they paired psilocybin with one of biology's wildest adversaries, the rabies virus.The virus, created by staff at the Allen Brain Science Institute in Seattle, would travel and follow a "very complex circuit" of the brain, Kwan said, like Google's mapping machines driving around every neighborhood.through the streets.

"With psilocybin, it's like we connect all these pathways to the brain, but we don't know where the pathways go," Kwan said. This is how they're made. It skips the synapse and goes from one neuron to another."

Key results of brain mapping

First, the researchers injected a single dose of psilocybin into the mouse's frontal cortical pyramidal neurons.Then, a day later, they chased it with a variant of the rabies virus that could transmit across the synapse and tag associated neurons with fluorescent proteins.After the virus had incubated in the mouse for a week, the team imaged its brain and compared the results to the brain of a control mouse that only received the virus.

The fluorescent tracer showed that psilocybin weakened recurrent connections in the cerebral cortex—feedback loops that may explain why a depressed person becomes attached to negative thoughts.

"Rumination is one of the hallmarks of depression, where people focus unhealthily and dwell on the same negative thoughts," Cowan said."By reducing attenuation, this cycle."

The researchers also found that the sensory region of the brain becomes stronger in the subcortical region, strengthening the connection between perception and action.

Future treatment options

Quan was initially expected to find a link between one or two brain regions of the brain, but was surprised to find that Psilocybin revival involved the entire brain.

"These are really brain-wide changes," he said."It's a scale we've never worked on before. Many times we focus on a small part of the neural circuitry."

A detailed road map also showed that the number of firing processes in the brain can be determined by the combination of the drug.This inspired the researchers to show that by disrupting and controlling one activity in one part of the brain, they could indeed change the course of the empy.

"This opens up many possibilities for treatment,

More details: Quan Kiang et al, Monlocybin shows functional modification of major food networks, Cell (2025).Work: 10,1016 / J.CEl.2025,1.009