Figure 6.

LC-regulated brain activation states. Refer to Figure 5 as legend for the representation of different brain areas. While many intermediate states are likely to exist, we depict in the sketch only four of them, in order of energy demand. During the sleep state (upper left) the LC is inactive, all cortices (except possibly limbic cortices) are virtually inactive, maintenance processes (like memory consolidation and basal immune activity) are on-going, while cellular energy content is restored. During quiet wake(upper right), LC is moderately active in the tonic mode, maximizing phasic release of NE which allows optimal intracortical communication and flexible behavioral and decision-making strategies and memory and learning associated with high phasic LC activation and βR-mediated activation. During high-energy demand (stress, lower left), an increased drive in the limbic cortex induces higher LC activation and hyperactivity in other cortical areas relevant to the specific stressor (most often the PFC, but on occasion could be other areas like motor or sensory cortices could be over-activated to carry out specific behavioral tasks). Extreme stress induces hyperactivity in parts of the limbic system, fight- or-flight response (lower right), overdrive and functional shut-down of the PFC, and hyper-activation of motor areas and subcortical nuclei (symbolized by the grid lines, MA: motor areas, SA sensory areas, SCN: subcortical nuclei, PFC: prefrontal cortex, LA: limbic areas, LC: locus ceruleus).