Johannes Bohacek
@bohaceklab.bsky.social
Dad. Associate Professor @ ETH Zurich. We study stress, behavior, hippocampus, noradrenaline and the mighty locus coeruleus. We work with mice and focus a lot on 3Rs.
Here to learn, share, laugh and rant.
Here to learn, share, laugh and rant.
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
January 20, 2026 at 9:16 PM
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
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...
January 14, 2026 at 2:05 PM
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...
Hahaha.... ah... great, thank you!! I will add it to my collection. You made my day 😊
January 12, 2026 at 4:40 PM
Hahaha.... ah... great, thank you!! I will add it to my collection. You made my day 😊
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?
January 6, 2026 at 10:49 AM
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.
January 6, 2026 at 10:49 AM
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! 🙏
StressomeExplorer2
ethz-ins.org
January 5, 2026 at 4:55 PM
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.
January 5, 2026 at 4:55 PM
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.
January 5, 2026 at 4:55 PM
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!
Great to have a brilliant bioinformatician!
January 5, 2026 at 4:55 PM
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!
Great to have a brilliant bioinformatician!
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.
January 5, 2026 at 4:55 PM
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.
January 5, 2026 at 4:55 PM
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.
Surprisingly, corticosterone still peaks normally in both sexes, despite strong transcriptional blunting, showing a disconnect between HPA axis and hippocampal gene expression.
January 5, 2026 at 4:55 PM
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.
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.
January 5, 2026 at 4:55 PM
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 🤯
January 5, 2026 at 4:55 PM
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 🤯
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 👇
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.
media.tenor.com
January 5, 2026 at 4:55 PM
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 👇