, 2011, Soc. Neurosci., abstract). The strength of dlPFC functions vary according to our state of arousal: working memory abilities are greatly impaired during fatigue or stress (Arnsten, 2009; Thomas, 2005), and even mild pressure can impair the ability to find insightful solutions to problems (Subramaniam et al., 2009). Our data indicate that there are ionic mechanisms that can cause rapid losses of dlPFC network excitation

while maintaining the architectural integrity of the immensely complex networks needed for mental representation. Thus, there can be a momentary weakness in dlPFC function (e.g., a potential stressor that takes dlPFC “off-line” and switches control of behavior to more habitual, subcortical mechanisms), quickly followed by a return selleckchem to more thoughtful, top-down dlPFC regulation when safety is assured. This dissociation between arousal effects on mental state and memory consolidation allows us to make new memories, even if the PFC is “off-line” click here during stress; for example,

high levels of catecholamines can simultaneously weaken dlPFC top-down regulation, while strengthening consolidation of the stressful experience through actions in amygdala, hippocampus, and sensory cortices. These dual actions in distinct brain circuits arise from differences in downstream intracellular signaling processes initiated by the modulatory arousal pathways. There are a large number of arousal pathways that project to the cortical mantle from the brainstem or ventral forebrain; for example, NE, dopamine (DA), serotonin, acetylcholine, GABA, histamine, and orexin neurons all project to the cerebral cortex, including the PFC.

There is also endogenous catecholamine production in the dlPFC of some primate species, including humans (Raghanti et al., 2009). The variations in locus coeruleus (LC) NE neuronal firing across arousal states has been extensively studied by Foote and Aston-Jones: LC neurons are silent during REM sleep, show little activity in deep sleep, have robust phasic activity to relevant stimuli during alert waking, and high, tonic firing during mild stress (e.g., Foote et al., 1983; Rajkowski et al., 2004). enough Several systems have been studied in primates performing cognitive tasks. Recordings from the NE or DA cell bodies indicate that NE and DA would be released in dlPFC in a phasic manner in anticipation of, or in response to, salient events associated with reward or aversion (Bromberg-Martin et al., 2010; Rajkowski et al., 2004; Schultz, 1998), while recordings from basal forebrain (Richardson and DeLong, 1986) or raphe (Okada et al., 2011) neurons suggest that acetylcholine and serotonin release would occur in more direct association with reward (aversive stimuli have not been studied).