Regulation of Cortical Functions by the Central Noradrenergic System: Emerging Properties from an Old Friend

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(VTA)-dopamine (DA) systems are two important brainstem neuromodulatory ascending pathways with a widespread cortical distribution. Historically, the NE system has been implicated in arousal whereas DA signals have been linked to reward and motivation. In addition to this early interpretation, recent findings indicate that the NE system also play an important role in the control of complex behaviors (Devilbiss and Waterhouse, 2004; Aston-Jones and Cohen, 2005a; Chamberlain et al., 2006). For example, neuronal activity in the LC, particularly the phasic firing mode, has been associated to the outcome of certain task-related decision processes, and it has been proposed that this enhancement of NE signal (presumably in the cortex) helps to optimize task performance (Aston-Jones and Cohen, 2005a). A similar pattern of firing response to task-related events has also been observed in DA neurons (Lidow et al., 1998). These data suggest that both NE and DA systems are responsive to motivationally salient events such as reward predictors.

The central NE system also plays a crucial role in determining the outcome of brain function in response to acute and chronic stress. Many neurochemical studies, in fact, have shown that NE is able to produce a stress response resulting from activation of the hypothalamus-pituitary-adrenal axis

In the past 20 years, extensive studies have been conducted to elucidate the role of LC NE during complex and specific behavioral performances and stress. Although the global effect of NE activation seems to lead to overall increases in neural responsiveness, alertness, and a temporary refinement of perceptual receptive fields, little is known about how NE receptors interact with other neural systems, in particular in brain regions involved in executive functions and cognition. In this chapter we will first review data from animal studies reporting the effects of NE on cortical neurons, and, secondly, we will summarize how NE-single cell interactions impact cortical functions by changing the behavior of cortical circuits.