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: 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...

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

Pain and welfare monitoring is essential for ethical animal testing, but current cage-side assessments are qualitative and subjective. Here we present the GrimACE, the first fully standardised and aut...

Arousal levels regulate sleep, but accurate noninvasive measures are lacking. Here, a novel method is introduced to track pupil-indexed arousal levels during human sleep, revealing pupil size changes ...

Pyramidal cells are classically thought to comprise the excitatory output of the subiculum. Here, the authors show the existence of “ovoid cells”, excitatory subiculum neurons with specialized gene ex...

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomi...

Norepinephrine oscillations during NREM sleep drive synchronized changes in cerebral blood volume and cerebrospinal fluid, promoting glymphatic clearance. Optogenetic and pharmacological manipulations confirm that vasomotion, regulated by norepinephrine, acts as a pump for brain fluid transport.

Can processes occurring in one individuals nervous system influence the physiology of the descendants? Here we explored the provocative hypothesis that parents sensation or perception of environmental...