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#noradrenaline

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Johannes Bohacek

🚨Happy to share our lab's latest work! 🚨 #neuroscience #noradrenaline #stress

In 2016 I wrote a grant, asking a simple question: Stress triggers massive transcriptional changes, which of them are dependent on noradrenaline (NA) signaling?

Today, we have the answer, but boy was this a journey. A 🧵 👇

biorxiv.org/content/10.1101/20

bioRxivNoradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expressionExposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains a major challenge. Here we combine RNA-sequencing with selective pharmacological, chemogenetic and optogenetic manipulations to isolate the contribution of the locus coeruleus - noradrenaline (LN-NA) system to the acute stress response. We reveal that NA-release during stress exposure regulates a large and reproducible set of genes in the dorsal and ventral hippocampus via β-adrenergic receptors. For a smaller subset of these genes, we show that NA release triggered by LC stimulation is sufficient to mimic the stress-induced transcriptional response. We observe these effects in both sexes, independent of the pattern and frequency of LC activation. Using a retrograde optogenetic approach, we demonstrate that hippocampus-projecting LC neurons directly regulate hippocampal gene expression. Overall, a highly selective set of astrocyte-enriched genes emerges as key targets of LC-NA activation, most prominently several subunits of protein phosphatase 1 (Ppp1r3c, Ppp1r3d, Ppp1r3g) and type II iodothyronine deiodinase (Dio2). These results highlight the importance of astrocytic energy metabolism and thyroid hormone signaling in LC mediated hippocampal function, and offer new molecular targets for understanding LC function in health and disease. ### Competing Interest Statement The authors have declared no competing interest.
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Danai Riga

Is there anything the can't do.?

“...activation of LC NEergic signaling during CFC memory encoding mediates engram early tagging in the mPFC and systems consolidation of remote memory“

Noradrenergic signaling mediates cortical early tagging and storage of remote memory | Nature Communications
nature.com/articles/s41467-022

NatureNoradrenergic signaling mediates cortical early tagging and storage of remote memory - Nature CommunicationsThe locus coeruleus norepinephrine system plays a role in various cognitive functions. Here the authors show that in mice, locus coeruleus to medial prefrontal cortex norepinephrine release and β1-AR signaling during contextual fear conditioning are critical for remote memory storage.
#systemsneuro#noradrenaline
Continued thread
Public
Danai Riga

With recent controversy and excitement in the world, next comes this gem on the role of the and in prediction error-based learning

biorxiv.org/content/10.1101/20

Here, the authors showed that during decision-making, differential responses of neurons match reward probabilities. Further, inhibition of the disrupted learning based on

This validates another causal role for heterogeneity /modularity that directly affects decision-making

bioRxivTwo types of locus coeruleus norepinephrine neurons drive reinforcement learningThe cerebral cortex generates flexible behavior by learning. Reinforcement learning is thought to be driven by error signals in midbrain dopamine neurons. However, they project more densely to basal ganglia than cortex, leaving open the possibility of another source of learning signals for cortex. The locus coeruleus (LC) contains most of the brain's norepinephrine (NE) neurons and project broadly to cortex. We measured activity from identified mouse LC-NE neurons during a behavioral task requiring ongoing learning from reward prediction errors (RPEs). We found two types of LC-NE neurons: neurons with wide action potentials (type I) were excited by positive RPE and showed an increasing relationship with change of choice likelihood. Neurons with thin action potentials (type II) were excited by lack of reward and showed a decreasing relationship with change of choice likelihood. Silencing LC-NE neurons changed future choices, as predicted from the electrophysiological recordings and a model of how RPEs are used to guide learning. We reveal functional heterogeneity of a neuromodulatory system in the brain and show that NE inputs to cortex act as a quantitative learning signal for flexible behavior. ### Competing Interest Statement The authors have declared no competing interest.
Public
Rebecca Hendrickson MD, PhD

Before I overthink my "first post"*:

Interests: medicine/neuroscience; biologic changes in & treatment for #PTSD, #TBI, and #LongCovid; #sleep & autonomic function; trauma; catecholamine (esp #noradrenaline ) regulation; climate change. #R programmer & stats by necessity.

Help me figure out who to connect with here?

*excluding posts on Twitter, Facebook, MySpace, Friendster, LiveJournal, and some BBS that I used to talk about nerdy books and play VGA planets back in high school....

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