Our understanding of the mechanisms regulating gene expression has been hampered by our limited knowledge of which transcription factors (TFs) bind where in the genome, which is highly cell type-speci...

The authors present the GrimACE, an automated cage-side system that uses computer vision to score mouse pain and behavior. The tool, which detects postsurgery pain and analgesic effects, enables repea...

During arousal and stress, the locus coeruleus (LC) releases noradrenaline (NA) throughout the brain, including hippocampus. It remains, however, unclear how LC activity contributes to the cellular response profiles observed during natural arousal. Here we directly compared effects of natural arousal and isolated LC activation in mouse CA1 using physiologically titrated optogenetics, combined with fiber photometry of NA and calcium signals, chronic two-photon imaging, and behavioral monitoring. We found that natural arousal robustly activated all three major cell types - astrocytes, pyramidal cells, and inhibitory interneurons - on a population level. In contrast, stimulation of the LC alone exerted a slow inhibitory influence on pyramidal cells and interneurons, with only a subset of interneurons exhibiting a transient activation by LC stimulation. Interneurons, but not pyramidal cells, segregated into functionally consistent LC-responsive subpopulations (activated vs inhibited) with distinct laminar positions in CA1. However, these LC-responsive subpopulations of interneurons did not reliably map onto response subpopulations defined by activity patterns during natural arousal. Astrocytes were strongly activated by both natural arousal and LC stimulation. However, single-cell responses of astrocytes to LC stimulation only partially aligned with their activity during natural arousal responses, indicating distinct driving forces across the two conditions. Together, these results show that LC-driven NA release produces distinct, cell-specific effects that do not align with hippocampal dynamics during natural arousal. Thus, our findings highlight the need to rethink how the locus coeruleus influences the main hippocampal cell types in vivo. ### Competing Interest Statement The authors have declared no competing interest. ETH Zurich, ETH-20 19-1 Swiss National Science Foundation, 310030_172889, 310030_204372, 310030B_170269, PZ00P3_209114 Botnar Research Center for Child Health Swiss 3R Competence Center Roche (Switzerland), https://ror.org/00by1q217 Hochschulmedizin Zürich Flagship project STRESS European Research Council, 670757

ALT: a man in a vest is dancing in a living room with a couch and chairs

ALT: an ad for jolt shows a linkedin logo in the clouds

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of mor...

Alt: This is a stupid GIF to point out that there are two mechanisms. But I want to qualify the statement about "no changes in baseline gene expression". They must be there, somewhere, but they are not visible in bulk - I suspect that they are either restricted to an extremely small percentage of cells, or to a cellular compartment (or both) - for which we lack the resolution and power - even with the snRNAseq data shown later.

Repeated stress triggers habituation, an important stress coping response. Here, authors chart the dynamic gene expression changes that underlie stress habituation in the mouse brain and reveal two di...

ALT: a man with long hair and a beard is saying it 's a morale builder isn 't it

Stress-induced depression-like behaviors are driven by a dynamic recurrent network involving neurons and astrocytes in the lateral habenula and norepinephrine release from neurons in the locus coerule...

A growing list of medications—such as zuranolone for postpartum depression, suzetrigine for pain, and the gepants class of migraine medicines—exist because of insights from basic research.

ALT: a man wearing a gas mask and a leather jacket is standing in front of a wooden building

The locus coeruleus (LC), the major source of norepinephrine (NE) in the brain, is among the earliest site of pathology in both Alzheimers disease (AD) and Parkinsons disease (PD), and it undergoes ca...

ALT: a group of people sitting in a theater with the words so hot right now written on the bottom