Mood, attention and motivation co-vary with activity in the neuromodulatory systems of the brain to influence behaviour. These psychological states, mediated by neuromodulators, have a profound influence on the cognitive processes of attention, perception and, particularly, our ability to retrieve memories from the past and make new ones. Moreover, many psychiatric and neurodegenerative disorders are related to dysfunction of these neuromodulatory systems. Neurons of the brainstem nucleus locus coeruleus are the sole source of noradrenaline, a neuromodulator that has a key role in all of these forebrain activities. Elucidating the factors that control the activity of these neurons and the effect of noradrenaline in target regions is key to understanding how the brain allocates attention and apprehends the environment to select, store and retrieve information for generating adaptive behaviour.

Mood, motivation, attention, and arousal are behavioral states having a profound impact on cognition. Behavioral states are mediated though the peripheral nervous system and neuromodulatory systems in the brainstem. The noradrenergic nucleus locus coeruleus is activated in parallel with the autonomic system in response to biological imperatives. These responses can be spontaneous, to unexpected salient or threatening stimuli, or they can be conditioned responses to awaited behaviorally relevant stimuli. Noradrenaline, released in forebrain structures, will facilitate sensory processing, enhance cognitive flexibility and executive function in the frontal cortex, and promote offline memory consolidation in limbic structures. Central activation of neuromodulatory neurons and peripheral arousal, together, prepare the organism for a reorientation or reset of cortical networks and an adaptive behavioral response.

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A memory trace in its active state is susceptible to interference by amnesic agents, such as hypothermia and electroconvulsive shock, and by NMDA receptor antagonists, suggesting that a time-dependent consolidation process occurs each time a memory is reactivated. The role of beta noradrenergic receptors in reconsolidation in rats was examined in both a positively reinforced radial maze task and a footshock-reinforced conditioned emotional response task. For the former, rats were trained over several days in a spatial reference memory task and received a single reactivation trial followed by propranolol. A temporally graded impairment was observed when propranolol treatment occurred after the memory reactivation trial. In the emotional task, memory impairing effects of propranolol were greater when the drug was administered after a reactivation trial than when administered immediately after the initial training. These results suggest that reactivation of memory triggers a beta receptor-dependent cascade of intracellular events, recapitulating that which occurs during initial postacquisition consolidation, thus permitting reorganization of the existing memory as a function of new information in the retrieval environment. This remarkable lability of an active memory trace provides a new basis for pharmacotherapeutic intervention in such syndromes as Posttraumatic Stress Disorder. beta adrenoreceptor antagonists may be promising pharmacological agents for attenuating debilitating memories at the time of their controlled reactivation.

Regulation of attention and promotion of behavioural flexibility are functions attributed to both the noradrenergic nucleus locus coeruleus (LC) and the prefrontal cortex (PFC). The PFC receives a large innervation from LC and small changes in catecholaminergic activity in PFC profoundly affect cognitive function. It is crucial to the understanding of learning-related plasticity, that the cognitive context driving LC neurons be determined and the relation to activity in PFC be elucidated. To this end simultaneous recordings were made from LC and prelimbic cortex (PL) during an odour-reward association task in the rat. Neuronal activity related to orientation of attention, reward predictability, reward itself, and changes in stimulus reinforcement contingencies, was measured. All LC neurons and a significant proportion of PL neurons were engaged during several aspects of a Go/NoGo task, especially after the signal for trial onset and CS+ presentation. LC activation was, however, more tightly aligned to the behavioural response than to the CS+ 22% of PL neurons were activated during the response-reward delay. This suggests that the activity of both these structures is related to reward anticipation. Finally, LC neurons exhibited rapid plasticity when the reward-contingency was modified. Within-trial response latencies were always shorter in LC than in PL and between-trial response adaptation in LC preceded that in PL by many trials. Identifying such temporal relationships is an essential step toward understanding how neuromodulatory inputs to forebrain networks might promote or permit experience-dependent plasticity in behavioural situations.

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