The following section reviews anatomical and physiological characteristics of the LC-NE system that have implicated the system in stress. More detailed information about this system and its other putative functions that are outside the scope of this review can be found in (Aston-Jones et al., 1995; Foote et al., 1983; Berridge and Waterhouse, 2003). The LC is a compact cluster of NE neurons in the pons that serves as the primary source of brain NE (Grzanna and Molliver, 1980). A distinguishing anatomical feature

of the LC is its widespread, highly collateralized projection system that innervates the entire neuraxis (Aston-Jones et al., 1995 and Swanson and Hartman, 1976). Through this axonal system the nucleus LC can broadly influence neuronal activity Cell Cycle inhibitor throughout the brain. Notably, the LC serves as the primary source of NE in forebrain regions such as the hippocampus and cortex that govern cognition, memory and complex behaviors. Selleckchem Fulvestrant The physiological characteristics of LC neurons have been studied in vivo in rodents and non-human primates and in vitro in slice preparations and have implicated this system in arousal, attention and behavioral flexibility (Aston-Jones and Bloom, 1981a, Aston-Jones and Bloom, 1981b, Foote et al., 1980, Williams and Marshall,

1987 and Aston-Jones and Cohen, 2005). LC neurons discharge spontaneously and their tonic rate is positively correlated to arousal state (Aston-Jones and Bloom, 1981b and Foote et al., 1980). However, the relationship between neuronal activity and arousal is more than just correlation because selective activation or inhibition of LC neurons results in cortical and hippocampal electroencephalographic (EEG) activation or inhibition, respectively, indicating causality between LC discharge rate and arousal (Berridge and Foote, 1991 and Berridge et al., 1993). As described below, LC activation is necessary for cortical EEG activation by stress (Page et al., 1993). In addition to spontaneous firing, Dichloromethane dehalogenase LC neurons are phasically activated

by salient, multimodal stimuli that elicit a burst of discharge followed by a period of inhibition (e.g., Fig. 1) (Aston-Jones and Bloom, 1981a), (Aston-Jones and Bloom, 1981a and Foote et al., 1980). The phasic response precedes orientation to the eliciting stimuli, suggesting that the LC-NE system redirects attention towards salient sensory stimuli. LC neurons are thought to discharge synchronously during phasic activation as a result of electrotonic coupling through gap junctions between dendrites outside of the nucleus, in the peri-coerulear (peri-LC) region (Ishimatsu and Williams, 1996). In contrast, during spontaneous or tonic LC discharge, the neurons are thought to be uncoupled (Usher et al., 1999).