The locus coeruleus and regulation of behavioral flexibility and attention: clinical implications

It has been proposed that the locus coeruleus (LC) regulates nonspecific arousal and thereby may participate in a wide range of functions. Our work indicates that, while the LC may indeed play an important role in arousal, it has more specific effects on behavior and may regulate cortical mechanisms involved in selective attention and task performance. In one study, we recorded impulse activity of LC neurons in monkeys performing a visual discrimination task. Phasic and tonic firing characteristics of LC neurons varied in close relation to task performance. Phasically, LC neurons were selectively activated by target cues and not by other task events, including behavioral responses. The target-elicited LC responses were limited to periods of good performance, when tonic firing rates were at an intermediate level (∼ 1 to 2 spikes/s). Higher levels of tonic activity were associated with few or no phasic LC responses, and poor task performance. Direct manipulations of LC activity via local microinfusions yielded behavioral results consistent with the above recordings. A computational model was constructed to explore mechanisms that underlie these patterns of LC activity and their relationship to task performance.1 This model revealed that electrotonic coupling among LC neurons can provide a mechanism for regulating the pattern of LC activity between two modes of functioning, which may in turn regulate task performance. In one mode (high electrotonic coupling, resulting in intermediate levels of tonic LC activity and robust phasic responses to task-defined target stimuli), LC responses facilitate the processing of target stimuli while responses to distractors are reduced. In the