Johannes Bohacek

Excited to share our new preprint! We explore the link between the locus coeruleus (LC) and arousal for astrocytes, pyramidal cells, interneurons in the hippocampus. A fantastic collaboration with @sianduss.bsky.social @bohaceklab.bsky.social, and many others: www.biorxiv.org/content/10.6... 1/5

Thanks David! All the props go to @ptrrupprecht.bsky.social who led all the cutting-edge and technically savvy analyses together with "my" freshly minted PhD superstar @sianduss.bsky.social

🔵 for all the locus coeruleus lovers: check out our latest work!

www.biorxiv.org/content/10.6...

🧵👇

I just registered for - exciting!!!

The "stress meetings" (alternating between North America and Europe) are my favorites in the conference cycle.

#stress2026

Weltschmerz

From my collection of powerful (and timely) German words.

Literally: World pain.

It refers to the suffering and pain one feels because of the state of the world and its inadequacy in relation to one's own desires and expectations.

very interesting, thanks for sharing your view on this. I didn't think of LinkedIn that way (you do a thing, you post it), but I get it. I miss the humor there, it seems awfully dry. But maybe that's just the bubble I (accidentally) created by not curating it over the years...

American colleagues: who of you uses LinkedIn for posting papers and preprints, to chat about research findings and stir the occasional controversy? In Europe LinkedIn seems to gain popularity amongst researchers, I just find it really sterile and all the posts too polished. Opinions?

Preprints of pandemic potential - new historical piece from me on the history of bioRxiv/medRxiv, their role in the pandemic, and the way forward. 1/n journals.asm.org/doi/10.1128/...

Hahaha.... ah... great, thank you!! I will add it to my collection. You made my day 😊

Day 7: A classic.

(the 3 people following this have now realized that there are long delays between my days...)

Day 6 of sharing gems from my personal cartoon collection. Share yours and make my day.

I like this one since I did my undergrad in psychology. And I'm Austrian, Sigmund Freud and all that stuff.

an ad for jolt shows a linkedin logo in the clouds ALT: an ad for jolt shows a linkedin logo in the clouds

I can't use twitter/X anymore, it's become an awful and useless place.

On this site here, I don't feel like I'm reaching the same colleagues I used to reach on twitter.

Someone just told me the action is on LinkedIn now. Really, LinkedIn!? Can I get some opinions on this? Are some of you there?

Mimicking opioid analgesia in cortical pain circuits - Nature The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of mor...

Hot off the @nature.com press!!
Our A-SOiD behavior library developed specifically for pain to quantify a new chemogenetic gene therapy that targets opioid circuit in ACC without addictive properties
@flybottleescape.bsky.social @cmu-neuroscience.bsky.social @cmu.edu
www.nature.com/articles/s41...

It's great that you manipulate Ttr directly and show that overexpression under Camk2a promoter can actually increase spine density 🤯. Any thoughts about the mechanism? It supposedly shuttles T4 from CSF to interstitial fluid. You think its function in neurons is thyroid hormone related?

Congratulations Marija! I just read the manuscript, very cool! I'm struck by Ttr. I also always ignored it because I thought it was choroid plexus "only" (and like you say in the paper it was presumed to be a contamination), but we also see it in excitatory neurons in our vHC single-nucleus data.

As always, we integrate these results with previously published bulk and single-cell data from our lab and make these data freely accessible and searchable through an interactive app (ethz-ins.org/stressome2). This is a very large resource, we hope people like it - please share! 🙏

In contrast, GR motifs open within 15min of stress exposure in all cells independent of the activation state of the cell. Across cells, GRE accessibility vanishes faster after chronic stress. This is showing a clear mechanistic difference between cAMP- and GR-dependent habituation.

Looking at genome accessibility separately in activated and inactivated cells provided mechanistic insight (thanks to reviewers!): CREB/SRF motifs spike only in activated neurons, but this response is blunted after chronic stress. cAMP-related habituation is thus linked to cellular activity.

By computing stress-induced activity scores for each cell, we find that fewer cells are recruited after CRS, not weaker activation per cell. VIP interneurons and CA1 neurons show the strongest drop in activation. Glial activation also halves after CRS.

Great to have a brilliant bioinformatician!

These terrible dimensionality reduction plots. But they show the beautiful resolution you get with this amount of nuclei, lots of clearly defined cellular populations emerge, both based on the snRNAseq and the snATACseq data.

Single-nucleus multi-omics on >160’000 cells (n=3/group) reveals cell-type-specific stress responses across time. Neurons react fast (VIP interneurons at 15min), glia sustain responses longer. CRS blunts these dynamics across cell types, highlighting widespread habituation.

Chromatin accessibility changes rapidly after acute stress (e.g., GR motifs), but repeated stress does NOT alter these patterns at baseline or after stress. Bulk ATAC-seq cannot explain transcriptional habituation, pointing to other mechanisms.

Similar to transcriptional habituation, behavioral changes (higher anxiety) emerge after 10 days of stress.

Surprisingly, corticosterone still peaks normally in both sexes, despite strong transcriptional blunting, showing a disconnect between HPA axis and hippocampal gene expression.

Temporal dynamics reveal different habituation patterns. The habituation of early response genes seems to rely on cAMP-related signaling and their expression is mimicked by forskolin (a cAMP activator). Genes that respond later are linked to glucocorticoid, they are also activated by dexamethosone.

Acute restraint triggers waves of transcription in the ventral hippocampus. After chronic stress, this response is globally blunted: virtually all stress-responsive genes show reduced activation. 10 or 20 days of restraint lead to similar habituation. A lot of info (and 192 brains) in this heatmap 🤯

two men with long hair and glasses are standing next to each other with the words " not one but two " on a green background Alt: This is a stupid GIF to point out that there are two mechanisms. But I want to qualify the statement about "no changes in baseline gene expression". They must be there, somewhere, but they are not visible in bulk - I suspect that they are either restricted to an extremely small percentage of cells, or to a cellular compartment (or both) - for which we lack the resolution and power - even with the snRNAseq data shown later.

Surprisingly, even after 3 weeks of chronic (daily) restraint stress (CRS) there is no change in baseline gene expression! However, the dynamic transcriptomic response to acute stress gets massively blunted. Two distinct mechanisms emerge, here’s the whole story in a nutshell 👇

Acute stress triggers a profound transcriptional response. How does this response change as stress becomes chronic?

We address this with multiomic profiling using daily restraint in mice. Led by Rebecca Waag and my bioinformatics partner in crime Pierre-Luc Germain. www.nature.com/articles/s41...

How does your favorite gene respond to stress? Check out our updated “Stressome-app”!

In a new @natcomms.nature.com paper we vastly extend our interactive app with loads of bulk and single-cell transcriptomics after acute and chronic stress. www.nature.com/articles/s41...

I'll walk you through👇

Extremely excited & proud to share our new preprint - we provide for the first time a single cell map of the mouse brain across sex, the estrous cycle, and peripartum! Data are 🔥 👇

"Single-cell map of the female brain across reproductive transitions"

www.biorxiv.org/content/10.6...

Day 5