alexkwan.bsky.social
Associate Professor at Cornell BME. Studying the neurobiology of psychiatric #drugs including #ketamine and #psychedelics.
https://alexkwanlab.org
173 posts
3,404 followers
1,283 following
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It's a newer journal but part of @acnporg.bsky.social so reputable and will grow
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As a Primer for @dpn-journal.bsky.social?
A growing society journal devoted to quantitative methods
Eg, pubmed.ncbi.nlm.nih.gov/39099890/ by @goldenneuron.bsky.social
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Just had time to watch - it’s so accessible and fun. I wish I could join in the ‘game show’ and win channelrhodopsin too 😀
I would love to have the slides to spread the word
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Thanks - hope to catch you another time!
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They said I just missed a couple cold and rainy weeks 🤞
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Too bad I missed you - it was a great visit
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Congrats on the massive undertaking. I particularly like the supplementary tables where you compared the effect sizes and variances.
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Overall, this effort reminded me of this excellent @simonsfoundation.org SFARI led study to characterize ASD mouse models comprehensively.
They could not replicate some earlier findings, and the effect size tends to be milder than what individual labs report
pubmed.ncbi.nlm.nih.gov/28753255/
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I wonder if how this assay choice affected the results from the preprint when they test the persisting effect via FST and TST.
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Another note -
For learned helplessness, initially we tested the same animal before and after drug, for a within-subject design in the 2021 Neuron paper. There may be confound because we saw hints that mice learn from the test for the re-test..
In the 2025 paper, we only did one test after drug.
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Though the authors cautioned about variability across labs. Seems to me that two labs did not see an effect, and two labs saw a mild effect. The final lab saw a large effect, which drove the pooled results.
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@samcwoodburn.bsky.social previously tested 2 mg/kg psilocybiin, among many other conditions, for fear extinction.
pubs.acs.org/doi/full/10....
The results are very close... Ours in the top, the cross-lab average in the bottom
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cc @ungteoriz.bsky.social who as you pointed out has done the pioneering work in this area.
One thing to note is the species difference. When we looked, the persistence is there but weaker in rodents.
pubmed.ncbi.nlm.nih.gov/30615132/
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The cake was also amazing, with pistachio cream inside 🤯
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You may be interested to know co-author Rong-Jian Liu was a long time colleague of George.
Rong-Jian contributed to Fig. 5d, which is exactly how George did many of his studies.
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George A's work was an inspiration, showing serotonin evokes excitatory currents in pyramidal cells.
Here we extend to show psilocybin's effects on one specific type of these pyramidal cells, and may be more importantly how it is important for the long-term plasticity and behavioral effects
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Bonus: A view-only link for the article: rdcu.be/ef9Nv
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We also wrote a short Research Briefing piece highlighting the key findings. Check it out here:
doi.org/10.1038/d415...
12/12
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The research is possible with funding from NIH/NIMH
Additional support from NIH/NIDA @onemindorg.bsky.social and the Source Research Foundation 🙏
A collaborative effort between my team at @cornellengineering.bsky.social, KAIST, and @aliciache.bsky.social at Yale Psychiatry 🤝
11/12
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To summarize: same receptor (5-HT2A), different circuits.
The short- and long-term effects of psilocybin are mediated by different circuits, with the PT neurons in frontal cortex sitting at the core of the long-term response.
10/12
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Moreover, deleting the serotonin 2A receptor specifically in PT neurons eliminates the psilocybin-evoked structural remodeling.
These are strong evidence supporting the role of serotonin 2A receptors in psychedelic drug action.
9/12
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Getting back to the receptor –
It has long been debated whether serotonin 2A receptor is needed. We took a precise approach, using a conditional knockout mouse to show that deleting the receptor in frontal cortex abolishes psilocybin’s long-term behavioral effects.
8/12
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And while the spiking response is heterogeneous, we find a subset of frontal cortical PT neurons that show strong activation following psilocybin administration.
7/12
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Digging deeper, there are other cell-type specific features.
Psilocybin increases calcium activity in the apical dendrites of PT neurons, but not IT neurons.
6/12
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Interestingly, neither the PT nor the IT manipulations affected the acute head-twitch response.
The results highlight PT neurons as key to the long-term antidepressant-like effects of psilocybin.
5/12
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But when it comes to behavior, the two cell types diverge.
Normally, psilocybin can reverse stress-related behaviors. When we inactivate PT neurons before administering psilocybin, the drug’s ameliorating effects disappeared. Silencing the IT neurons had no effect.
4/12
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To start, we look at structural plasticity.
After a single dose of psilocybin, both PT and IT neurons in the medial frontal cortex sprout new dendritic spines, indicating neural remodeling.
3/12
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Pyramidal cells in the neocortex are not all the same. There are major PT (pyramidal tract) and IT (intratelencephalic) subtypes. Interestingly, both subtypes express the serotonin 2A receptor 🧬.
What roles do they play for psilocybin’s action?
2/12
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My heart goes out to all of the good folks within NIH who are dealing with shit more directly.
I am so sorry that you, your colleagues, and the institution that you love are being treated with such disrespect.
4/n
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Love the sketches (and the talk looks fun too) @crisniell.bsky.social
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Congrats on the publication! This is a really cool finding, and I’ve shared the preprint with others.
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It was mentioned as a pitfall as early as here
pmc.ncbi.nlm.nih.gov/articles/PMC...
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Very exciting - just heard @nicolecrust.bsky.social lauded your work as the future for developing a better understanding of neuropsychiatric disorders. Agree 💯
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This is a great piece, and all very true