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 found partial anatomical segregation between the LC to pontine reticular nucleus (PRN) and LC to basal forebrain (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 pivotal role for early LC->PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a prominent role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.
An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening
