Summary/Abstract Ascending acetylcholinergic and noradrenergic neuromodulatory systems are thought to alter information processing in cerebral cortex with spatial and temporal precision (Obermayer et al., 2017). Yet we lack basic information about how these systems affect neural responses underlying perception and decision-making in sensory cortex of awake, behaving subjects. The overarching goal of this project is to investigate how cholinergic and noradrenergic inputs to visual cortex are activated during a visual detection task. Genetically coded neurotransmitter reporters (GRAB-Ach, GRAB-NE) are novel tools that can measure local neurotransmitter concentrations in cortex with sub-second resolution. These newly developed genetically coded neurotransmitter reporters offer an unprecedented window into real-time changes in local neurotransmitter concentration during perceptual decision-making. Aim 1 will define the relationship of ACh and NE neurotransmitter concentrations in primary visual cortex to behavioral decision variables. Aim 2 will define the relationship of ACh and NE neurotransmitter concentrations in primary visual cortex to the fidelity of the neural representation. This work will provide preliminary data for larger scale studies that examine the effect on neurotransmitter concentrations of manipulating cognitive variables such as attention, decision-making, and working memory. These initial experiments will set the stage for future studies that manipulate neurotransmitter concentrations with systemic or intracranial drug injections to test causal relationships between neurotransmitters and behavioral performance.