RT Journal Article SR Electronic T1 Activation of neuromodulatory axon projections in primary visual cortex during periods of locomotion and pupil dilation JF bioRxiv FD Cold Spring Harbor Laboratory SP 502013 DO 10.1101/502013 A1 Rylan S. Larsen A1 Emily Turschak A1 Tanya Daigle A1 Hongkui Zeng A1 Jun Zhuang A1 Jack Waters YR 2018 UL http://biorxiv.org/content/early/2018/12/19/502013.abstract AB Neuromodulators such as acetylcholine, noradrenaline (norepinephrine), and serotonin are released into the cortex by axons ascending from subcortical nuclei. These neuromodulators have been hypothesized to influence cortical function during behavioral periods such as arousal, locomotion, exploration, and attention. To determine when these neuromodulatory projections were active, we expressed the genetically-encoded calcium sensor GCaMP6 in neuromodulatory axons which project to the mouse primary visual cortex and performed two-photon microscopy to monitor their activity in vivo. We observed that the fluorescence of both cholinergic and noradrenergic axons increased during periods of pupil dilation, with the fluorescence of the axons rising less than one second before eye pupil dilation. We also observed increases in cholinergic and noradrenergic axon fluorescence periods of locomotion, which was accompanied by pupil dilation and nasal (forward) movement of both pupils. Locomotion was preceded by a rise in axonal fluorescence with a timing and amplitude that matched the subsequent pupil dilation, but axon fluorescence was more sustained than expected from the pupil dilation, suggesting that there is an additional physiological factor that affects cholinergic and noradrenergic axon activity in primary visual cortex during locomotion.