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#locuscoeruleus

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Happy & proud to share our latest work with the #bluespot community, #locuscoeruleus enthusiasts, and anyone else willing to read 😉

biorxiv.org/content/10.1101/20

4 years ago, we had the idea that endogenous neuromodulatory systems are in place that control LC activity, thereby promoting adaptive behavioral responses in challenging environments.

We examined the role of Neuropeptide Y, as a possible candidate system for this, and identified a new population of #NPY-expressing neurons, distributed in the pericoerulean space.

We showed that peri-LC NPY cells innervate the region, providing #NPY input onto #noradrenergic neurons of the LC, and strongly inhibiting their activity, via Y1Rs.

Next, we showed that chemogenetic stimulation of NPY cells led to anxiety-relief, via Y1Rs, and conversely, inhibition of NPY neurons triggered an anxiogenic phenotype.

Together, we showed a novel role for NPY-mediated #neuromodulation of the LC in adaptive behaviors.

We re happy to hear your thoughts /ideas /feedback on our data.

Please share/boost. Happy reading 🔵

bioRxiv · Neuropeptide Y neurons of the locus coeruleus inhibit noradrenergic system activity to reduce anxietyAdaptive responses to challenging environments depend on optimal function of the locus coeruleus (LC), the main source of noradrenaline in the brain and primary mediator of the initial stress response. Built-in systems that exert regulatory control over the LC are largely unidentified. A good candidate system is neuropeptide Y (NPY), which is traditionally linked to anxiety-relief. Currently, the endogenous source of NPY to the LC, and how NPY-expressing neurons modulate the noradrenergic system to regulate anxiety remain unclear. We here identify, in mice, a novel NPY-expressing neuronal population (peri-LCNPY) neighboring LC noradrenergic neurons that locally innervates the pericoerulean space. Moreover, we demonstrate that stress engages peri-LCNPY neurons, increasing their excitability. Mimicking peri-LCNPY neuronal activation using ex vivo chemogenetics suppresses LC noradrenergic neuron activity, via an NPY Y1 receptor-mediated mechanism. Furthermore, in vivo chemogenetic stimulation of peri-LCNPY neurons results in Y1R-dependent anxiety-relief. Conversely, inhibiting peri-LCNPY neurons increases anxiety-like behaviors. Together, we establish a causal role for peri-LCNPY-mediated neuromodulation of the LC in the regulation of anxiety, providing novel insights in the endogenous mechanisms underlying adaptive responses to adversity. ### Competing Interest Statement The authors have declared no competing interest.
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Across these datasets (>200 mice tested), we find that BFA increases statistical power and reveals phenotypes that would otherwise be missed.

The snapshot below shows an example where we were underpowered (n=8) to detect treatment effects (DREADD activation of the #LocusCoeruleus), but BFA unveils the latent phenotype! 🔵

Plugging here for fellow #bluespot member & #locuscoeruleus enthusiast, Greyson Sipe:

"the Sipe lab officially started at Penn State in March, 2023 and we are actively recruiting graduate students and postdoctoral fellows! Please feel free to spread the news to anybody interested in studying neurons, astrocytes, and neuromodulators in arousal, stress and addiction. The lab is pretty much set up with a cutting-edge 2-photon microscope, a custom 1-photon widefield scope, two dual-color fiber photometry rigs, and a suite of behavioral rigs with optogenetics (mini-scopes are on the way)".

For inquiries check:
sipelab.com/openings

Sipe LaboratoryOpportunities — Sipe Laboratory

New instance, new #introduction!
I am a psychologist, turned behavioral neuroscientist, turned electrophysiologist. Finishing my postdoc @ meyelab.net/ and soon to start @ mcn.cncr.nl/ NL

I am interested in all things #circuits, #patching, #stress and the incredible #locuscoeruleus

You ll find me knitting, baking & complaining, most times, simultaneously.

Looking forward to meet, listen & learn.

meyelab.netResearchOur research focuses on afflictions of the nervous system in which reward seeking plays a key role. Stress causes changes at specific synapses Research FJ Meye