Adrenergic Modulation of Cortical Gain and Sensory Processing in the Mouse Visual Cortex

Background/Objectives: Sensory perception is influenced by internal neuronal variability and external noise. Neuromodulators such as norepinephrine (NE) regulate this variability by modulating excitation-inhibition balance, oscillatory dynamics, and interlaminar connectivity. While NE is known to modulate cortical gain, it remains unclear how it shapes sensory processing under noisy conditions. This study investigates how adrenergic modulation affects signal-to-noise processing and perceptual decision-making in the primary visual cortex (V1) of mice exposed to varying levels of visual noise. Methods: We performed in vivo local field potential (LFP) recordings from layers 2/3 and 4 of V1 in sedated mice to assess the impact of visual noise and systemic administration of atomoxetine, a NE reuptake inhibitor, on cortical signal processing. In a separate group of freely moving mice, we used a two-alternative forced-choice to evaluate the behavioral effects of systemic and intracortical adrenergic manipulations on visual discrimination. Results: Moderate visual noise enhanced cortical signal processing and visual choices, consistent with stochastic resonance. High noise levels impaired both. Systemic atomoxetine administration flattened the cortical signal-to-noise ratio function, suggesting disrupted gain control. Behaviorally, clonidine impaired accuracy at moderate noise levels, while atomoxetine reduced discrimination performance and increased response variability. Intracortical NE infusions produced similar effects. Conclusions: Our findings demonstrate that NE regulates the balance between signal amplification and noise suppression in a noise- and context-dependent manner. These results extend existing models of neuromodulatory function by linking interlaminar communication and cortical variability to perceptual decision-making.