iiinova — where your digital self keeps evolving

Reposted by Nick Petersen

Maddy Jalbert @maddyjalbert.bsky.social · 31/01/2025

I am one of these NSF postdocs. NSF has frozen everyone’s access to their salaries and research stipends (that were already awarded) with no information about when they might be expected to be unfrozen. It still appears like we are expected to continue doing our work though.

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Reposted by Nick Petersen

Sam Centanni @samcentanni.bsky.social · 08/01/2025

Hello Bluesky! 👋 Excited to join this community. Interested in what the lab is working on? Instead of spending an hour perfecting/overthinking my first post, here's something even better: our lab's very first preprint! Just uploaded to @biorxiv-neursci.bsky.social www.biorxiv.org/content/10.1...

biorxiv.org

A stress-activated mid-insula to BNST pathway regulates susceptibility to abstinence-induced negative affect in female mice

Stress is central to many neuropsychiatric conditions, including alcohol use disorder (AUD). Stress influences the initiation and continued use of alcohol, the progression to AUD, and relapse. Identif...

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Huge thanks to my mentor @dgordonwinder.bsky.social, our amazing collaborators (@davidweinshenker.bsky.social, Kate McCann, Mihaela Stavarache), and everyone who made this work possible!

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Our work highlights a complex astrocyte-neuron communication network that fine-tunes arousal by integrating noradrenergic signals to amplify wake-promoting circuits. This adds another example of astrocyte heterogeneity, given that astrocytes in other regions have been implicated in sleep promotion.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Finally, we show this mechanism in vivo. While adenosine and A2A activation usually promote sleep, we found that in the vPAG, A2A activity is necessary for the wake-promoting effects of α1AR activation—adding nuance to how we think about norepinephrine and adenosine’s roles in sleep-wake regulation.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Astrocytes are known to release gliotransmitters, such as adenosine. Blocking adenosine A2A receptors prevented α1AR and Gq-DREADD activation from increasing dopamine neuron excitability. We also saw increased A2A mRNA expression in the triple-α1AR KD mice, suggesting a compensatory upregulation.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

What about vPAG astrocytic triple α1AR knockdown in vivo? We saw no differences in several behavioral and metabolic parameters… EXCEPT for an increase in sleep time during the dark cycle (when mice are usually awake)! This suggests these receptors are important specifically for maintaining arousal.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Given that multiple α1AR subtypes are expressed on astrocytes, we designed an AAV that expresses shRNAs to knockdown the 3 α1AR subtypes in vPAG astrocytes – it worked surprisingly well! This dampened α1AR-induced calcium increases in the dopamine neurons and prevented the increase in excitability.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

From our Porter-Stranksy led study, we knew that Gq-DREADD activation (mimicking α1ARs) of vPAG astrocytes increases wakefulness in vivo, but now we know it likely does so by increasing the dopamine neuron excitability and activity.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Using ex vivo calcium imaging, we show that activating α1ARs in the vPAG increases calcium activity in the wake-promoting dopamine neurons and astrocytes. α1AR activation also significantly increased the excitability of the dopamine neurons. 🔬

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Here, we propose a model of how astrocytes contribute to arousal through downstream activation of dopamine neurons via adenosine A2A receptors.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

Sleep & arousal are fundamental, but we still don’t fully understand how they’re regulated. Led by Kirsten Porter-Stransky, we previously showed that activation of alpha1 adrenergic receptors (α1ARs) in the vPAG increases wakefulness and that these receptors are highly expressed on vPAG astrocytes.

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Nick Petersen @nickpetersen.bsky.social · 13/01/2025

I’m pumped to share that our new paper in Biological Psychiatry is out! We dissected a novel astrocyte-neuron interaction in the ventral periaqueductal gray (vPAG) that maintains wakefulness involving norepinephrine and dopamine neurons🧵: www.biologicalpsychiatryjournal.com/article/S000...

biologicalpsychiatryjournal.com

Adenosine A2A Receptors Link Astrocytic α1-Adrenergic Signaling to Wake-Promoting Dopamine Neurons

Sleep and arousal disorders are common, but the underlying physiology of wakefulness is not fully understood. The locus coeruleus promotes arousal via α1-adrenergic receptor (α1AR)–driven recruitment ...

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