Abstract
Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species. However, the physiological processes linking cortical state and pupil variations are largely unknown. Here we demonstrate that these rapid variations, during both quiet waking and locomotion, are highly correlated with fluctuations in the activity of corticopetal noradrenergic and cholinergic projections. Rapid dilations of the pupil are tightly associated with phasic activity in noradrenergic axons, whereas longer-lasting dilations of the pupil, such as during locomotion, are accompanied by sustained activity in cholinergic axons. Thus, the pupil can be used to sensitively track the activity in multiple neuromodulatory transmitter systems as they control the state of the waking brain.
Highlights
Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species
Pupil size has been widely assumed to be a reliable indicator of activity in the locus coeruleus (LC)[8,9] and cortical state is powerfully controlled by the release of acetylcholine (ACh)[10,11,12] and norepinephrine (NE)[13,14,15]
Activity in NE and ACh projections in layer 1 (L1) of wakeful mice was highly coherent with pupil fluctuations, at frequencies between 0.03 and 0.4 Hz for noradrenergic axons and o0.03 Hz for cholinergic axons (Fig. 1h and Supplementary Fig. 1C,D; example traces, Fig. 1d–h and Supplementary Figs 2–4)
Summary
Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species. We demonstrate that these rapid variations, during both quiet waking and locomotion, are highly correlated with fluctuations in the activity of corticopetal noradrenergic and cholinergic projections. Rapid fluctuations in pupil diameter are highly correlated with alterations in electrophysiologically measured brain states, neural responsiveness and behavioural performance[4,5,6,7]. We studied the relationship of activity in cholinergic or noradrenergic axons in the neocortex in relation to spontaneous alterations in arousal (pupil diameter) and locomotion. We find that activity in noradrenergic projections in cortex tracks the phasic changes in pupil diameter better than the cholinergic terminals. Cholinergic projections showed more tonic activation when the pupil was dilated for a longer time such as during locomotion
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