Changes in pupil diameter that reflect effort and other cognitive factors are often interpreted in terms of the activity of norepinephrine-containing neurons in the brainstem nucleus locus coeruleus (LC), but there is little direct evidence for such a relationship. Here, we show that LC activation reliably anticipates changes in pupil diameter that either fluctuate naturally or are driven by external events during near fixation, as in many psychophysical tasks. This relationship occurs on as fine a temporal and spatial scale as single spikes from single units. However, this relationship is not specific to the LC. Similar relationships, albeit with delayed timing and different reliabilities across sites, are evident in the inferior and superior colliculus and anterior and posterior cingulate cortex. Because these regions are interconnected with the LC, the results suggest that non-luminance-mediated changes in pupil diameter might reflect LC-mediated coordination of neuronal activity throughout some parts of the brain.
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