The role of the LC-NE system in attention: From cells, to systems, to sensory-motor control

Attention control is a fundamental cognitive function that enables individuals to sustain focus, shift attention flexibly, and filter distractions in a goal-directed manner. The locus coeruleus-norepinephrine (LC-NE) system plays a pivotal role in this process by dynamically regulating arousal, prioritizing salient stimuli, and optimizing cognitive performance. This review synthesizes evidence from molecular, cellular, systems, cognitive neuroscience, and behavioral studies to elucidate the LC-NE system's role in attention control. We first examine the neurophysiological mechanisms of the LC, highlighting its distinct firing patterns-tonic and phasic activity-and their impact on attention. Next, we integrate findings from animal models, human neuroimaging, electrophysiology, and computational modeling, demonstrating how LC-NE activity influences sensory processing, cognitive flexibility, and executive function. We interpret these findings through the lens of three major theoretical frameworks: Adaptive Gain Theory (AGT), which describes how LC activity optimizes task engagement, the Network Reset Hypothesis (NRH), which describes how optimizes network connectivity, and the Glutamate Amplifies NE Effects (GANE) model, which explains how NE enhances neural selectivity and suppresses irrelevant signals. Collectively, the evidence underscores the LC-NE system's role in modulating the signal-to-noise ratio in cortical and subcortical circuits, thereby shaping attention and behavior. We conclude by discussing implications for individual differences, age-related cognitive decline, and emphasizing the need for interdisciplinary research that integrates emerging technologies to further unravel the complexities of LC function.