An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening
Data files
Sep 09, 2025 version files 137.82 MB
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doubleGRABne_table.mat
77.48 MB
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README.md
2.19 KB
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retroGCaMP7s_table.mat
60.35 MB
Abstract
The locus coeruleus norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit-specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the LC→PRN and LC→BF circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-ChR2 activation or PdCO silencing of synapses in target regions, revealed a role for early LC→PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a role for early LC-NE PRN activity in connecting sensory and arousal pathways, and establish LC heterogeneity in regulating arousal.
Dataset DOI: 10.5061/dryad.nzs7h453f
Description of the data and file structure
Files are stored in matlab (.mat) format, and represents fiber photometry recordings during sound evoked awakening experiments.
The sound was a broad band noise lasting 1s, as described in Methods section. All the data are from NREM sleep, and trials are divided by outcome- either maintained sleep or awakening.
Each row represents a single trial, with information on the mouse ID, the trial outcome, the ROI if relevant, the time (from -2 to 3 s around sound onset), and the normalized delta f/f. Normalizaion included detrending and normalizing the full data stream to the isosbestic channel, and a subtraction of the 5 second baseline from each trial. For more details go to the methods section.
Files and variables
File: doubleGRABne_table.mat
Description: WT mice (n=7) were injected with GRAB(NE) in both BF and PRN and fiber photometry was recorded simultaneously from the two areas during natural sleep. The data is the normalized delta f/f GRAB(NE) recordings from the PRN and from the BF that were recorded simultaneously. This data corresponds with Fig. 2.
Variables
- mouse ID (“dblGRAB1”/ ”dblGRAB10”/ ”dblGRAB11”/ ”dblGRAB12”/ ”dblGRAB3”/ ”dblGRAB5”/ ”dblGRAB9”)
- outcome (maintained / awakening)
- time (s)
- deltaF/F BF
- deltaF/F PRN
File: retroGCaMP7s_table.mat
Description: DBH-Cre mice were injected with AAVretro vectors encoding a Cre-dependent GCaMP7s in the PRN and BF (n(PRN)=7, n(BF)=7) and bulk calcium activity was recorded in the LC corresponding sub-population. This data corresponds with Fig. S3.
Variables
- mouse ID (“LC_BF1”/ “LC_BF2”/ “LC_BF3”/ “LC_BF5”/ “LC_BF6”/ “LC_BF7”/ “LC_BF8”/ “LC_PRN1”/ “LC_PRN4”/ “LC_PRN5”/ “LC_PRN6”/ ”LC_PRN7”/ ”LC_PRN8”/ ”LC_PRN9”)
- ROI (BF/ PRN)
- outcome (maintained / awakening)
- time (s)
- deltaF/F
Code/software
To view the data, files need to be opened in MATLAB.