Thanks Ewan!
Thanks Ewan!
Project led by trio of @felipedefaria.bsky.social, Gabriela Basile Carballo and @melisa-mc.bsky.social, involving collaborators @liu.se Håkan Olausson and Max Larsson. Exciting research is possible thanks to our funders @kawresearch.bsky.social , @vetenskapsradet.bsky.social, Hjarnfonden. 8/8
Zooming out to understand the structure. Mechano-nociceptive pathways are organized hierarchically: nociceptor subtypes are recruited according to tissue and organ context. Mapping these ensembles gives a framework for decoding peripheral representations of pain across the body. 7/8
Surprisingly, expression analysis indicated that subset of Adm+ neurons expressing Uts2b+ were activated only by bladder distension. Can nociceptors be indeed organ-selective? We used a Uts2b:Cre line to confirm that projections of Uts2b+ nociceptors are confined to the bladder. 6/8
Next, we turned to less-studied A-fiber nociceptors. Here we identified Adm+ A-fibers and showed that they were preferentially recruited by visceral stimuli, indicating that fast mechano-nociceptive signaling is also organized by tissue domain. 5/8
Then, we tested the C-fiber nociceptors component. Ensemble composition changed only modestly across an array of skin stimuli. In contrast, representation of cutaneous vs visceral pressure diverged strongly, with Adra2a+ C-fibers dominating response to bladder and colorectal distension. 4/8
To compare nociceptive signaling across submodalities and locations, we focused on lumbosacral dorsal root ganglia, whose neurons innervate both skin and pelvic organs. But first, we built a functional and transcriptomic map of these neurons as a reference. 3/8
This is hard to study because it’s difficult to see which combination of nociceptor classes is activated in vivo during noxious stimulation. We used the calcium integrator CaMPARI to label stimulus-activated neurons, allowing us to profile nociceptive ensembles with single-cell RNA-seq. 2/8
Not all pain is created equal: stepping on a nail feels different from a stomachache. We know there are many nociceptor types, but a key question remains: how is mechanical pain encoded across the body by those sensory neurons? Our new work helps answer this. 1/8
www.biorxiv.org/content/10.6...
A read only for the DRG nerd: "Spatial organization, chromatin accessibility and gene-regulatory programs defining mouse sensory neurons". www.nature.com/articles/s42...
Not a season unfortunately! Next time surstromming is on us.
It was a pleasure to host Ewan at our Linköping University LinkSense seminar series! We learned a lot about joints — and even managed to gossip a bit about naked mole rats. Always a good time.
Red farmhouse in green fields
Cows having breakfast
Me standing surrounded by trees halfway round
Flew in late last night to visit @szczotml.bsky.social
& co @liu.se - looking forward to an exciting day discussing touch & pain - early morning 🏃🏻♂️ = ✅ = 🕸️ 🧹
Thank you for visitng, great experience.
Congratulations, amazing.
Thank you Melisa, It has been a fascinating journey on an uncharted road. It is official now we have the first Lab Alumni! Little sour/sweet feeling TBH. Good luck in your new adventures.
Finally, we managed to take a lab picture
I really think one of the best things about science is the people you meet along the way. Thanks @mbrodzki.bsky.social,Gabriela, Leandro, Christoffer and Felipe!Especially thanks to @szczotml.bsky.social and Ilona,I really enjoyed all our discussions!
Now, I'm very excited about what's coming next!
Thanks Ted! Exciting and fun work.