Neuromodulatory Systems and Their Interactions: A Review of Models, Theories, and Experiments

Neuromodulatory systems, including the noradrenergic, serotonergic, dopaminergic, and cholinergic systems, track environmental signals, such as risks, rewards, novelty, effort, and social cooperation. These systems provide a foundation for cognitive function in higher organisms; attention, emotion, goal-directed behavior, and decision-making derive from the interaction between the neuromodulatory systems and brain areas, such as the amygdala, frontal cortex, hippocampus, and sensory cortices. Given their strong influence on behavior and cognition, these systems also play a key role in disease states and are the primary target of many current treatment strategies. The fact that these systems interact with each other either directly or indirectly, however, makes it difficult to understand how a failure in one or more systems can lead to a particular symptom or pathology. In this review, we explore experimental evidence, as well as focus on computational and theoretical models of neuromodulation. Better understanding of neuromodulatory systems may lead to the development of novel treatment strategies for a number of brain disorders.