Thread by @0xQuasark

Science just did the unthinkable:

Researchers genetically modified the world's deadliest virus to trace how psilocybin physically repairs the brain...

𝗱𝗼𝘄𝗻 𝘁𝗼 𝘁𝗵𝗲 𝙚𝙭𝙖𝙘𝙩 𝗻𝗲𝘂𝗿𝗼𝗻𝘀 𝗶𝗻𝘃𝗼𝗹𝘃𝗲𝗱.

We've finally figured out why one trip can change your entire life 🧵

Here's the problem scientists had:

Since 2021, we've known that psilocybin grows new connections between brain cells. Thousands of them. And they last for weeks.

𝗕𝘂𝘁 𝗻𝗼𝗯𝗼𝗱𝘆 𝗸𝗻𝗲𝘄 '𝘄𝗵𝗲𝗿𝗲' 𝘁𝗵𝗼𝘀𝗲 𝗰𝗼𝗻𝗻𝗲𝗰𝘁𝗶𝗼𝗻𝘀 𝘄𝗲𝗿𝗲 𝗴𝗼𝗶𝗻𝗴. Which brain regions were wiring to which 𝘰𝘵𝘩𝘦𝘳 regions?

That question just got answered by a team at Cornell.

They needed a way to trace connections backward through the brain - to light up every neuron sending signals into a specific area.

The solution?
𝗔 𝗺𝗼𝗱𝗶𝗳𝗶𝗲𝗱 𝗿𝗮𝗯𝗶𝗲𝘀 𝘃𝗶𝗿𝘂𝘀.

Rabies naturally travels backward through your nervous system.

It jumps from one nerve cell into every cell connected to it → then those cells → then those cells.

But scientists at the Allen Institute engineered a version 𝘁𝗵𝗮𝘁 𝗼𝗻𝗹𝘆 𝗷𝘂𝗺𝗽𝘀 𝗼𝗻𝗰𝗲.

Delete one gene, add a green fluorescent marker, and you have a neural tracer!

Here's how the experiment worked:

𝗗𝗮𝘆 𝟭: Inject helper virus into frontal cortex of mice, to prime neurons.
𝗗𝗮𝘆 𝟭𝟰: Give psilocybin (1mg/kg) to one group or saline as a control.
𝗗𝗮𝘆 𝟭𝟲: Inject the modified rabies virus into the same brain region.
𝗗𝗮𝘆 𝟮𝟭: Rabies has spread backward one connection. Harvest the brain.

They used light-sheet microscopy to photograph every slice.

Machine learning counted every glowing cell - over 500,000 input neurons per mouse brain.

Each cell 𝗺𝗮𝗽𝗽𝗲𝗱 𝘁𝗼 𝗶𝘁𝘀 𝗲𝘅𝗮𝗰𝘁 𝗹𝗼𝗰𝗮𝘁𝗶𝗼𝗻 across 316 different brain regions.

The first complete map of psilocybin's rewiring.

What they found was shocking.

The rewiring wasn't random. It followed a specific pattern based on brain networks.

Statistical significance: p = 0.00006

The probability this pattern happened by chance? 𝟲 𝗶𝗻 𝟭𝟬𝟬,𝟬𝟬𝟬.

𝗖𝗼𝗻𝗻𝗲𝗰𝘁𝗶𝗼𝗻𝘀 𝘁𝗵𝗮𝘁 𝗴𝗼𝘁 𝗦𝗧𝗥𝗢𝗡𝗚𝗘𝗥 (+10%):

Primary somatosensory cortex - what you feel on your skin (touch, pain, temp)
Primary visual cortex - what you see.
Retrosplenial cortex - spatial memory and your sense of self.
Motor cortex - movement.

Every region processing sensory information from the outside world.

𝗖𝗼𝗻𝗻𝗲𝗰𝘁𝗶𝗼𝗻𝘀 𝘁𝗵𝗮𝘁 𝗴𝗼𝘁 𝗪𝗘𝗔𝗞𝗘𝗥 (-15%):

Infralimbic area - fear responses.
Orbital frontal cortex - expectations and decision-making.
Insular cortex - internal body state, anxiety.
Hippocampus - memory.
Amygdala - emotional processing.

Every region that process information about YOU.

Your memories. Your fears.
Your internal emotional state.

Your brain became less focused on itself.

The weakened regions form the default mode network - the system active when you're ruminating, mind-wandering, fixating on negative thoughts.

𝗗𝗲𝗽𝗿𝗲𝘀𝘀𝗶𝗼𝗻 𝗹𝗶𝘃𝗲𝘀 𝗶𝗻 𝘁𝗵𝗲𝘀𝗲 𝗹𝗼𝗼𝗽𝘀.
Psilocybin physically reduced their influence.

Then came the breakthrough that changed everything.

They used a drug to silence one brain region during the psilocybin trip.

When that region was silenced?
Its connections didn't get rewired.

𝗕𝘂𝘁 𝗲𝘃𝗲𝗿𝘆 𝗼𝘁𝗵𝗲𝗿 𝗮𝗰𝘁𝗶𝘃𝗲 𝗿𝗲𝗴𝗶𝗼𝗻 𝘀𝘁𝗶𝗹𝗹 𝗴𝗼𝘁 𝗿𝗲𝘄𝗶𝗿𝗲𝗱 𝗻𝗼𝗿𝗺𝗮𝗹𝗹𝘆.

Here's what that means:

Psilocybin only rewires the parts of your brain that are firing while the drug is active.

Whatever you're experiencing during those hours - what you're seeing, thinking, feeling - that's what gets wired into your brain permanently.

The rewiring isn't random.
𝗜𝘁'𝘀 𝗽𝗿𝗼𝗴𝗿𝗮𝗺𝗺𝗮𝗯𝗹𝗲.

And now we know 𝘄𝗲 𝗰𝗮𝗻 𝗰𝗼𝗻𝘁𝗿𝗼𝗹 𝘄𝗵𝗮𝘁 𝗴𝗲𝘁𝘀 𝗿𝗲𝘄𝗶𝗿𝗲𝗱.

Want to strengthen visual processing pathways? Show specific images during the trip.

Want to weaken anxiety circuits? Use brain stimulation to quiet the fear center while psilocybin is active.

We could design the rewiring instead of letting it happen randomly.

Lead researcher Alex Kwan put it simply:

'𝘠𝘰𝘶 𝘤𝘰𝘶𝘭𝘥 𝘢𝘷𝘰𝘪𝘥 𝘵𝘩𝘦 𝘣𝘳𝘢𝘪𝘯 𝘤𝘩𝘢𝘯𝘨𝘦𝘴 𝘵𝘩𝘢𝘵 𝘢𝘳𝘦 𝘯𝘦𝘨𝘢𝘵𝘪𝘷𝘦 𝘢𝘯𝘥 𝘦𝘯𝘩𝘢𝘯𝘤𝘦 𝘴𝘱𝘦𝘤𝘪𝘧𝘪𝘤𝘢𝘭𝘭𝘺 𝘵𝘩𝘦 𝘰𝘯𝘦𝘴 𝘵𝘩𝘢𝘵 𝘢𝘳𝘦 𝘱𝘰𝘴𝘪𝘵𝘪𝘷𝘦.'

This isn't just psychiatry anymore.
𝗜𝘁'𝘀 𝗯𝗿𝗮𝗶𝗻 𝗽𝗿𝗼𝗴𝗿𝗮𝗺𝗺𝗶𝗻𝗴.

They used a virus that would kill you to figure out how a mushroom can heal you.

For the first time in history, we're not just watching the brain change.

𝗪𝗲 𝗰𝗮𝗻 𝗰𝗵𝗼𝗼𝘀𝗲 𝘄𝗵𝗮𝘁 𝗶𝘁 𝗯𝗲𝗰𝗼𝗺𝗲𝘀.

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I break down any new psychedelic news.

Read the full article here 👇
cell.com/cell/fulltext/…