More Than Meets the Eye: Unravelling the Pupil’s Link to Brain State

It is a poetic cliché that the eyes are the windows to the soul, yet neuroscientists have long preferred to view them as precise gauges for the brain’s engine. Specifically, fluctuations in pupil size are known to track with arousal and the activity of the locus coeruleus (LC), a small but mighty nucleus in the brainstem responsible for releasing norepinephrine. However, a recent study suggests this relationship is far more nuanced than a simple cause-and-effect loop.

Investigating awake mice, researchers utilised optogenetics—a method using light to control neurons—to stimulate the LC directly. They then compared the brain’s electrical activity (EEG) during this artificial stimulation against moments of spontaneous pupil dilation. The findings were stark: the cortical states were not identical. Using advanced machine learning to analyse the data, the team discovered that while the pupil dilated in both scenarios, the brain’s internal rhythm differed significantly, particularly within the Gamma frequency band.

The plot thickened when the team introduced pharmacological agents to block or stimulate specific adrenergic receptors. They found that alpha and beta receptors play distinct roles in fine-tuning the coupling between the pupil and the cortex. This implies that the LC-norepinephrine system does not merely act as a master switch for alertness but orchestrates a complex symphony of neural states. Understanding these mechanisms is vital for decoding how our brains process information during varying levels of arousal.