We observed a similar phenomenon in an odor discrimination task during reversal learning or during an intradimensional shift in which the rat had to learn new odor pairs (Bouret and Sara, 2004). In a recent series of experiments in monkeys, we examined the relation of LC activity as a function of Pavlovian and instrumental responses emitted in the same reward schedule task (Bouret and Richmond, 2009). The activation of LC neurons was systematically associated with Pavlovian appetitive responses (lipping), which occurred both at the time of cue onset this website and at the time of instrumental responses (bar

release). Thus, even if LC activation coincides with the initiation of a goal-directed action, it seems to be related to an underlying Pavlovian

behavioral response. Note that Pavlovian autonomic responses were also observed around goal-directed actions (Collet GDC-0068 supplier et al., 1997; Amiez et al., 2003). Altogether, these data raise the possibility that LC activation in this and other cognitive tasks is strongly dependent upon the neuronal structures that control the concomitant autonomic activation. LC neurons fire when the organism faces a behaviorally significant stimulus, either a threat to be avoided, a foe to be fought, or a reward to be obtained, and the activation occurs in parallel with physiological reactions and primitive behavioral reflexes that allow a rapid, stereotyped response to the challenge. An anatomical model to account for the simultaneous activation of LC and the multiple physiological manifestations of the orienting response has been proposed recently, suggesting that LC and the peripheral nervous system are activated

by a common input from the NPG (Nieuwenhuis et al., 2010; Pfaff et al., 2012). Thus, LC activation might be considered as part of a general orienting reflex that includes physiological responses such as changes in heart rate, respiration, and pupil dilation, elicited by behaviorally significant stimuli or unexpected changes in the environment. According to early investigators, electroencephalogram (EEG) desynchronization and pupil dilation always accompany the orienting reflex. In fact, eye movement toward the source of the stimulus, from which the name “orienting reflex” is MycoClean Mycoplasma Removal Kit derived, is completely dependent on the level of EEG arousal and degree of dilation of the pupil. When EEG is synchronized and the pupils constricted, there is no eye movement to the stimulus, i.e., no behavioral manifestation of the “orienting reflex” (Sokolov, 1963). Thus, it appears that the cortical arousal is related to the behavioral reflex, in this case, eye movement. This strong relation between arousal and behavioral components of the orienting reflex is further supported by a recent experiment in which pupil dilation could be elicited directly by an electrical stimulation of the superior colliculi, which play a critical role in behavioral orienting responses (Wang et al., 2012).