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Cortical processing is dynamically modulated by different neuromodulators. Neuromodulation of the cerebral cortex is crucial for maintaining cognitive brain functions such as perception, attention and learning. However, we do not fully understand how neuromodulatory projections are organized in the cerebral cortex to exert various functions. The basal forebrain (BF) cholinergic projection and the locus coeruleus (LC) noradrenergic projection are well-known neuromodulatory projections to the cortex. Decades of studies have identified anatomical and physiological characteristics of these circuits. While both cholinergic and noradrenergic neurons widely project to the cortex, they exhibit different levels of selectivity. Here, we summarize their anatomical and physiological features, highlighting selectivity and specificity of these circuits to different cortical regions. We discuss the importance of selective modulation by comparing their functions in the cortex. We highlight key features in the input-output circuits and target selectivity of these neuromodulatory projections and their roles in controlling four major brain functions: attention, reinforcement, learning and memory, sleep and wakefulness.

Function of Selective Neuromodulatory Projections in the Mammalian Cerebral Cortex: Comparison Between Cholinergic and Noradrenergic Systems