DOI: 10.5061/dryad.nzs7h453f
title: An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening

description: 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.
description: # An early surge of norepinephrine along brainstem pathways drives
 sensory-evoked awakening Dataset DOI:
 [10.5061/dryad.nzs7h453f](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.