ReviewCatecholamine Influences on Dorsolateral Prefrontal Cortical Networks
Section snippets
Top-Down Regulation by Prefrontal Cortex
The PFC intelligently regulates our thoughts, actions, and emotions through extensive connections with other brain regions, including projections to the association cortices for the regulation of sensory processing (8) and extensive projections to the basal ganglia and cerebellum for the regulation of motor, cognitive, and emotional responses (9) (Figure 1). The PFC creates a mental sketch pad through networks of neurons that maintain information in the absence of environmental stimulation (10
The Key Role of Prefrontal Cortical Networks in Representational Knowledge
The PFC is able to represent information that is not currently in the environment through networks of pyramidal neurons that excite each other to maintain information in mind. The circuitry underlying representational knowledge in PFC has been most intensively studied in the visuospatial realm, in monkeys performing a spatial working memory task (Figure 2A). In this task, the monkey has to maintain the memory of a precise spatial location over a delay period before moving its eyes to the
The Strength of Network Connections Is Rapidly Altered by the Neurochemical Environment: Integrating Arousal and Cognition
The arousal pathways (e.g., norepinephrine, dopamine, acetylcholine, serotonin, histamine, and orexins) all project to the PFC, and it is likely that all influence PFC function (26). However, a long history of research on the catecholamines has advanced our knowledge of these mechanisms in particular. This research began with the landmark discovery that depletion of catecholamines from the dorsolateral PFC was as detrimental as ablation of the cortical tissue itself (4). It is now known that
The Underappreciated Role of Norepinephrine
Although much of the previous research on ADHD and PFC has focused on DA mechanisms, recent data indicate that NE mechanisms are just as important and may even have more utility for the development of medications because of distinct NE actions at adrenergic receptors. Norepinephrine has the highest affinity for α2 adrenergic receptors and lower affinity for α1 and β receptors (34). Therefore, the type of receptor engaged may be determined by the amount of NE release.
Data from studies of monkey
The Complex Roles of DA
It has long been appreciated that DA is essential to the working memory functions of the PFC (4). New research is now revealing the contribution of DA to orbital PFC functions as well, which appears to differ from serotonergic actions (96) (26). The current article focuses on DA actions in dorsolateral PFC during spatial working memory, given this has been best studied at the cellular level.
There are two families of DA receptors: the D1 (D1 or D5) and D2 (D2, D3, D4) families of receptors. The
Conclusions
There has been remarkable progress in our understanding of PFC circuits and their relevance to ADHD. Studies of catecholamine actions on dorsolateral PFC microcircuitry have revealed intricate and powerful mechanisms to regulate the strength of persistent neuronal firing and the degree of neuronal tuning. Given the complexity and precision of these mechanisms, it is not surprising that problems with PFC regulation are prevalent in many neuropsychiatric disorders. As NE and DA mediate the
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