Rose Bagot

Had a great time visiting USyd! Thanks for hosting me @nataliematosin.bsky.social

Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus Nature Communications - Corticotropin-releasing hormone (CRH), known for activating the HPA axis during stress, also acts centrally in the brain. Here, the authors show that CRH modulates thalamic...

Happy to announce our new paper in Nature Communications: rdcu.be/eBpGY
We show how CRH in the thalamic reticular nucleus modulates NREM sleep, helping to understand how stress impacts sleep

Congrats to Loredana Cumpana and team, in work led by Simone Astori!
@epfl-brainmind.bsky.social‬

False positives in study of memory-related gene expression - Nature Nature - False positives in study of memory-related gene expression

Important 'Matters Arising' from @neurome.bsky.social and Zhaoxia Yu discussing false positives due to multiple comparisons in large-scale gene expression data. I applaud Eran and others who consistently raise these issues for discussion in the community.

www.nature.com/articles/s41...

Sam Weiss speaking #unfiltered at the CAN-ACN EDI session. Make more jobs for Canadians! @canacn.bsky.social

To all those descending onto Toronto for the @canacn.bsky.social annual meeting, as program chair I hope you have an exciting meeting and enjoy our featured speakers @franklandlab.bsky.social
@yulonglilab.bsky.social @neurovoice.bsky.social @turrigiano.bsky.social and Kerry Ressler #CAN2025

#resilience2025 fantastic speaker line-up: Andrew Holmes, Moh Milad, Dominique de Quervain @dequervain.bsky.social, Birgit Kleim, Rose Bagot @rcbagot.bsky.social, Floris Klumpers, Patricia Molina @pmolinamolina.bsky.social, Marianne Müller, Penny Lewis, Niels Niethard @nniethard.bsky.social, ...

Systems consolidation reorganizes hippocampal engram circuitry Nature - A study shows that loss of memory precision associated with systems consolidation can be explained by neurogenesis-dependent reorganization of engram circuitry within the hippocampus over...

Sharing a new paper from the lab. This paper, led by Sangyoon Ko, represents a merging of two longstanding research themes in the lab-- adult neurogenesis and systems consolidation.

rdcu.be/el18q

A short thread follows for those interested.

1/n

If you are in Toronto on Tuesday next week, please consider coming to see a FREE public lecture on memory, delivered by the amazing @sjo09.bsky.social and @barense.bsky.social . Tix at this link can-acn.org/meeting-2025... Please repost and hope to see you there!

Whole brain dimensional approach identifies shared and sex-specific networks of stress susceptibility in male and female mice. Background: Stress is a significant risk factor for depression and anxiety, two highly comorbid disorders with sex differences in symptom presentation and prevalence. The Chronic Variable Stress (CVS)...

Really excited to share this new preprint led by senior PhD student Liz Herrera Portillo who is co-supervised by
@rcbagot.bsky.social
!!

We use longitudinal MRI to show that mice exposed stress undergo sex-specific neuroanatomical reorganization.

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

Looking forward to exploring exciting new directions together!

Reward integration in prefrontal-cortical and ventral-hippocampal nucleus accumbens inputs cooperatively modulates engagement - Nature Communications Neural circuit mechanisms underlying integrating information about reward across time are not fully understood. Here, the authors show that common outcome-integration signals from the medial...

Thrilled to see this part of my PhD work with @rcbagot.bsky.social now out in @natcomms.nature.com!
(1/14)

www.nature.com/articles/s41...

Schematic of the experiment

Our latest work led by @claraliao.bsky.social is a collaboration with the other Kwan lab @kwanlab.bsky.social

We used single-nucleus RNA sequencing to measure transcriptional responses in the mouse medial frontal cortex following a single dose of psilocybin. 🍄 🧠 🧬

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

This work was co-led by post-doc Delong Zhou and grad student Heike Schuler- both yet to land in Bsky. Big thank you to some of the funders that supported this work @ludmercentre.bsky.social and @hbhlmcgill.bsky.social

Taken together, this work points to L5/6NP neurons as a key mediator of psilocybin’s neuroplastic effects. Our findings suggest that integrated 5-HTR signaling mediates acute cell-type specific responses to psilocybin that lead to sustained remodeling of mPFC neuronal network activity.

Finally, we examined differential gene expression. We find that psilocybin induces cell-type specific transcriptional programs associated with synaptic plasticity, upregulating synaptic genes in L5/6 NP and GABAergic neurons while increasing activity associated genes in L2-6 IT and L6 CT neurons.

We then examined cell-cell communication and find that psilocybin predominantly alters communication between neurons, suppressing GABAergic neuron signaling to all excitatory neurons.

This predicts that, psilocybin will primarily activate L5/6 NP neurons while suppressing all other excitatory neurons. We also saw interesting patterns in GABAergic sub-types that predict overall reduction of GABAergic suppression of excitatory neurons.

We find that L5/6 NP neurons are unique among excitatory neurons in that a large number of these neurons only express genes for excitatory 5-HT receptors, predominantly 5-HT2C. In contrast, all other excitatory neuron types predominantly express uniquely inhibitory 5-HT receptor genes.

Single-cell sequencing methods are prone to ‘technical drop-outs’ so not optimal for definitively mapping co-expression identity of at the single-cell level. We used spatial transcriptomics data sets to rigorously map cell-type specific expression and co-expression of a wide range of 5-HT receptors.

Neurons express many 5-HT receptors and psilocin binds these too. We hypothesized that the integrated expression patterns of excitatory and inhibitory 5-HT receptor genes might explain the specific sensitivity of L5/6 NP neurons.

Using an algorithm for cell-type prioritization, we show that a type of deep layer near projecting neuron – L5/6 NP - is most robustly regulated 24h after psilocybin. Interestingly, these neurons are not enriched for the gene encoding 5-HT2A. So why are they especially sensitive to psilocybin?

We used single-cell RNA sequencing to discover which mPFC cell types psilocybin impacts in female mice. We chose single cell over single nucleus RNAseq, which although more technically demanding in brain, can more accurately detect cellular state changes and differential transcriptional regulation.

This differential impact of sex on acute and delayed behavior supports findings suggesting distinct mechanisms mediate the hallucinogenic and neuroplastic effects of psilocybin.

First, we show that, while acutely, psilocybin similarly induced head twitch response in male and female mice, 24h later, psilocybin only reduced anxiety-like behavior in female mice.

New lab preprint ! There is a lot of excitement about the therapeutic potential of psilocybin but what is the mechanism? A beautiful body of work from @alexkwan.bsky.social shows that PFC plasticity is important. But how does this unfold and in which cell types?

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