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Lewis Holt @lewisholt.bsky.social · 26d

Congrats 👏!

Reposted by Lewis Holt

Ciarán Murphy-Royal @murphyroyallab.org · Sep 4

Thanks Bruno Geoffroy @crchum.bsky.social for the nice write up on our recent publication with @lewisholt.bsky.social

nouvelles.umontreal.ca/en/article/2...

After early-life stress, astrocytes affect behaviour

Canadian researchers show that stress modifies the morphology of brain cells in mice, directly influencing the rodents’ level of physical activity.

nouvelles.umontreal.ca

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Lewis Holt @lewisholt.bsky.social · Aug 6

Congrats Silvia! Looks great 😊

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Lewis Holt @lewisholt.bsky.social · Aug 5

Super psyched to help close out the #AstrocyteCafe on thursday!

Astrocyte Cafe @astrocytecafe.bsky.social · Aug 5

Join us this Thursday for the last #AstrocyteCafe session of this edition!!!

Looking forward to hearing the talks by Rowy Avishek,
@lewisholt.bsky.social and
@astrocytenet.bsky.social !😍😎

Register for our free mailing list or email us to get the link ;)

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Lewis Holt @lewisholt.bsky.social · Jul 14

Thanks! 😄 @joscience.bsky.social

Lewis Holt @lewisholt.bsky.social · Jul 11

This all came online while we were at @gliameeting.bsky.social 2025 meeting! I couldn't think of a better community to celebrate it with and in a better setting than the south of France!

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Lewis Holt @lewisholt.bsky.social · Jul 11

I want to give a big shout out to all the people in the CMR lab that helped with this project over the past few years, including those not on the paper. 💙

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Lewis Holt @lewisholt.bsky.social · Jul 11

10. Astrocytic glucocorticoid receptor deletion correct the excitability changes we saw after ELS in a sex specific manner! The remarkable thing was that these changes were sufficient enough to rescue the behavioural deficits caused by ELS back in Fig.1!

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Lewis Holt @lewisholt.bsky.social · Jul 11

9. Given the changes in blood CORT, we questioned if all these changes in running activity, firing rates and morphology could be a result of stress signalling in astrocytes? To get at this we selectively delete glucocorticoid receptors in astrocytes.

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Lewis Holt @lewisholt.bsky.social · Jul 11

8. In ELS female mice we observed deficits in lactate availability. We also used some cool intracellular sensors to look at lactate dynamics in LH neurons after ELS!

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Lewis Holt @lewisholt.bsky.social · Jul 11

7. We then got into what was underlying the divergent effects on orexin neuron firing in male and female mice. – Males first. Long story short, we saw elevated P2X receptor signalling was driving the hyper-excitability after ELS.

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Lewis Holt @lewisholt.bsky.social · Jul 11

6. By chemogenetically manipulating astrocyte activity, we could recapitulate the behavioural and cellular phenotypes we saw after ELS - see paper for all the data!

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Lewis Holt @lewisholt.bsky.social · Jul 11

5. But what about astrocytes after ELS? We saw changes in GFAP and Cx43. But to look at astrocyte morphology we developed a sparse viral labeling technique, which gave beautiful reconstructions of astrocytes in the LH. ELS shrunk astrocytes with a pronounced effect on branching in females!

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Lewis Holt @lewisholt.bsky.social · Jul 11

4. This behavioural phenotype was nicely reflected at the neuronal level in the lateral hypothalamus, where ELS male orexin neurons had increased firing rates and hyper-excitability and ELS female orexin neurons had reduced firing rates and hypo-excitability.

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Lewis Holt @lewisholt.bsky.social · Jul 11

3. We next found that ELS had opposing effects on running wheel behaviour across the light-dark cycle. Males ran more in their light phase and females ran less in their dark phase!

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Lewis Holt @lewisholt.bsky.social · Jul 11

2. Firstly, replicating the findings from previous work in the lab, we see mice that experience ELS (maternal separation 4hr / day + limited bedding) display much higher nadir levels of blood corticosterone, the primary stress hormone in rodents!

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Lewis Holt @lewisholt.bsky.social · Jul 11

1. Globally, this work builds on the growing body of literature investigating the effects of Early-Life Stress (ELS) on astrocytes, neuronal excitability and behaviour. This time we focused on astrocytes in the lateral hypothalamus.

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Lewis Holt @lewisholt.bsky.social · Jul 11

Absolutely thrilled to share the first half of my PhD work! Super proud to see it finally out!
www.nature.com/articles/s41...

Thread below for a quick (10 point) recap of what we found!
🧵🧪🧠

A divergent astrocytic response to stress alters activity patterns via distinct mechanisms in male and female mice - Nature Communications

Early-life stress has lifelong impacts on neuronal function and behavior. Here, the authors show that astrocytic glucocorticoid receptor signaling drives stress-induced neuronal and behavioral change ...

www.nature.com

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Lewis Holt @lewisholt.bsky.social · Jul 11

Thanks!! @dibenedetto-lab.bsky.social

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Reposted by Lewis Holt

Ciarán Murphy-Royal @murphyroyallab.org · Jul 11

Final leg of the Tour de France done with an excellent @gliameeting.bsky.social !
Amazing science in a great city, (despite some smoke!) and a nice travel award for @lewisholt.bsky.social 🥳

Going to make sure we come back to this meeting again next time! #glia2025

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Lewis Holt @lewisholt.bsky.social · Jun 14

Have to get you an above-ground pool to finish off that QC aesthetic!

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Lewis Holt @lewisholt.bsky.social · May 20

Thanks @paulsheppard.bsky.social !

Lewis Holt @lewisholt.bsky.social · May 20

Was great to present at @canglia.bsky.social today!
Cool to see all the glial research happening across Canada!

CANGlia @canglia.bsky.social · May 20

@lewisholt.bsky.social sharing some cool data about astrocytes driving stress-induced behaviour! #astroglia

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Reposted by Lewis Holt

Alex Chen @alexbchen.bsky.social · May 16

Excited to share that the astrocyte-centered half of my thesis work is now out @science.org ! With @mishaahrens.bsky.social and @marcduque.bsky.social
science.org/doi/10.1126/... 1/8

Norepinephrine changes behavioral state through astroglial purinergic signaling

Both neurons and glia communicate through diffusible neuromodulators; however, how neuron-glial interactions in such neuromodulatory networks influence circuit computation and behavior is unclear. Dur...

science.org

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Reposted by Lewis Holt

Papouin Lab @ WashU @papouinlab.bsky.social · May 16

Thought this would be a nice way to enter the bsky community👇Delighted for Katie (now in Chris Dulla's lab at Tufts). Thank you to our collaborators, to the reviewers and to Cagla Eroglu for the highlight!
www.science.org/doi/10.1126/...

Norepinephrine signals through astrocytes to modulate synapses

Locus ceruleus (LC)–derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit functional connectivity, but the underlying synapse-level...

www.science.org

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