Alex Kwan

Most definitely, I look forward to your images on Fridays!

Thank you! We try hard to get it right.

Thank you - this work definitely got us thinking more about drug action at the network scale.

For sure - the platform for the viral tracing and whole-brain imaging can be readily applied to other drugs.

I would love to know also how this compares with ketamine, other psychedelics, and related drugs.

Quan Jiang

This was a team effort spearheaded by Quan Jiang.

With help from collaborators at UC Irvine, CUHK 🇭🇰, and @alleninstitute.org, and support from @onemindorg.bsky.social and NIMH.

12/12

Activity modulation can steer the drug-induced plasticity.

2) We demonstrate that neural activity modulation may be a promising approach to sculpt the psychedelic-evoked neural plasticity.

11/12

Network connectivity changes after psilocybin administration.

Two main conclusions:

1) Psilocybin induces network-specific plasticity.

There was strengthened routing of inputs from RSP (mouse homolog of default mode network) and perceptual regions to subcortical targets. Meanwhile, inputs that are part of cortico-cortical loops were weakened.

10/12

Chemogenetic inactivation can change psilocybin-induced plasticity

If neural activity influences whether a region undergoes remodeling after psilocybin treatment, can we causally manipulate this plasticity?

We show this is possible - chemogenetic silencing of RSP disrupted psilocybin’s ability to strengthen those inputs.

9/12

Neuropixels recording of frontal cortex-projecting RSP neurons.

To investigate this possibility, we focused on one presynaptic region – the retrosplenial cortex (RSP).

Neuropixels recording confirms that indeed RSP neurons that project to frontal cortex fire more in response to psilocybin.

8/12

Relating c-Fos signals to rabies tracing results.

What drives this pattern of psilocybin-induced circuit remodeling?

One clue came from whole-brain c-Fos mapping, which correlated well with the input changes, suggesting neural activity in the presynaptic regions may play a role.

7/12

Tracing psilocybin's effect on inputs to frontal cortical neurons

We also traced from IT pyramidal cells, which interestingly have opposing changes in input fraction after psilocybin. What were strengthened for PT tend to be weakened for IT, and vice versa.

6/12

Tracing psilocybin's effect on inputs to frontal cortical neurons

The regions were not random though, increased inputs came from regions belonging to specific cortical networks, while decreases were inputs originating from other networks.

5/12

Tracing psilocybin's effect on inputs to frontal cortical neurons

Our initial hypothesis was that psilocybin may boost inputs from one or few regions. We would identify those key regions…

Surprisingly, tracing from PT pyramidal cells, our results show more widespread changes with inputs from many regions altered after psilocybin administration.

4/12

We would inject psilocybin or saline, then used monosynaptic rabies viruses to trace the input cells to the frontal cortical pyramidal neurons.

The whole-brain images were beautiful!
🔴 starter cells. 🟢 input cells.

(early #FluorescenceFriday - my favoriate hashtag)

Figure in a grant proposal to One Mind

The idea was to find circuits that are altered by #psychedelics, going beyond simply an increase of dendritic spines.

In the grant proposal, this figure was exactly how I pitched to @onemindorg.bsky.social, who believed in the vision and provided the critical early support for the project.

2/12

Summary figure for study of psilocybin's effect on cortical network connectivity.

New preprint + thread 🧵

#Psychedelics induce the formation of new synapses, but where do they connect?

Our rabies tracing study reveals that #psilocybin shifts connectivity across specific cortical networks.

www.biorxiv.org/content/10.1...

1/12

Serotonin drives choice-independent reconfiguration of distributed neural activity Serotonin (5-HT) is a central neuromodulator which is implicated in, amongst other functions, cognitive flexibility. 5-HT is released from the dorsal raphe nucleus (DRN) throughout nearly the entire f...

🚨Pre-print alert🚨

We stimulated serotonin with optogenetics while doing large-scale Neuropixel recordings across the mouse brain. We found strong widespread modulation of neural activity, but no effect on the choices of the mouse 🐭

How is this possible? Strap in! (1/9) 👇🧵

doi.org/10.1101/2025...

5
Concatenating primate brains based solely on their size provides a 1st striking illustration of the importance of mechanical morphogenesis: despite jumping across far branches of the phylogenetic tree, the sequence is largely continuous, hinting at a common underlying organising principle.

New preprint from collaboration with @sn-lab.bsky.social - 2p imaging of psilocybin's effects on neurovascular coupling 🧠🔬

We found that psilocybin prolongs the neurovascular response, independent of neural activity.

This would affect how we should interpret fMRI BOLD studies of psychedelics ‼️

Reply by Levine in 1967.

It appears to be their only paper on psychedelics.

There was a reply in the same year, suggesting nothing special about the blue color. The sample probably has psilocin as well. Similar to how psilocybe mushroom turns blue - here the brain tissue provides the enzymes needed for the blue to emerge.

Richard (Dick) O’Brien was a biochemist, and one of the people instrumental in creating the Department of Neurobiology and Behavior (NBB) at Cornell a few years earlier in 1964.

In this psilocybin paper, he proudly noted his NBB affiliation.

static.as.cornell.edu/150/nbb.html

Abstract for Gilmour and O'Brien, 1967

Gilmour and O’Brien mixed psilocybin with brain tissues enriched in synapses and mitochondria, they saw the mixture turned blue.

The paper was one of the earliest attempts to understand how a psychedelic interacts with the brain at a biochemical level.

Psilocybin: Reaction with a Fraction of Rat Brain Psilocybin, a hallucinogen, formed a blue color with a subfraction of rat-brain mitochondria believed to contain nerve-ending particles. Color formation increased with pH, did not require oxygen, and ...

Over the weekend, I stumbled upon a forgotten study from 1967 that was likely the first paper about psychedelics from Cornell University. 🤔

“Psilocybin: Reaction with a Fraction of Rat Brain” by Gilmour and O’Brien.
www.science.org/doi/10.1126/...

I had a great time at the first GRC psychedelics earlier this month! It was an amazing opportunity to learn about different aspects of research with psychedelics and discuss new data with many brilliant people! Can’t wait for 2027! #GRCPsychedelics

YouTube video by Steve Lawson Kara Marshall PHD-History of Science in America - Trilogy at Tehaleh 04/27/25

Watched @karalmarshall.bsky.social gave a similar talk and she had some great slides

I fully agree with this take. People get hung up on what the head-twitch response is or is not as a behavior.

It’s more useful to think of head-twitch response as a drug development tool.

RNAscope with probes for white matter (green) and relevant cell type markers in the striatum (magenta) in tissue section of human brain at the level of the ventral striatum

smFISH to validate anatomical level and localize nucleus accumbens for molecular profiling experiments in tissue sections of the human 🧠. I really love looking at the striations in the white matter of the internal capsule here - so satisfying! Image credit to Staff Scientist Svitlana Bach 👩‍🔬🧪🤩

Had a fantastic time at the Neurobiology of Psychedelics GRC. Only a week yet feels like it could have been months. New community, new lab, novel and diverse ideas and perspectives, unpublished brand new research, a lot of growth. Easily one of my favourites #GRCPsychedelics

Dispatch: The Neurobiology of Psychedelics Gordon Research Conference — Plasticity, Psychotherapy, and Perception (Part 1) - Psychedelic Alpha Here, we share Dr. Alaina Jaster’s observations from the inaugural Neurobiology of Psychedelics Gordon Research Conference, where leading scientists gathered to explore various realms of psychedelic…

Check out my keynote & Day 1 dispatch of #GRCPsychedelics 🧠 via @psychedelicalpha.bsky.social

psychedelicalpha.com/news/dispatc...

Congrats on the awards!