The locus coeruleus and noradrenergic modulation of cognition

Abstract

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.

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

“…The hypothesis that the LC-NE system contributes to P3 generation during a target detection task is consistent with the allocation of attentional resources and arousal effects in humans [13,[17][18][19]. Monkey studies with the oddball paradigm have shown that the conditions for generating the P3 are highly similar to those for the LC phasic response: both are preferentially elicited by attended, task-relevant, arousing, and salient stimuli that are important for goal-directed behavior [15,20].…”

“…The P3 component is thought to originate from neuronal inhibitory signals that inhibit unrelated neural activity to promote processing efficiency of task-relevant stimuli, thereby yielding large P3 amplitudes [13]. Correspondingly, activation of the LC-NE system in response to an important stimulus sends a "network reset" signal to the brain that interrupts the activity of the ongoing functional networks and facilitates their reorganization to promote rapid behavioral adaptation [18,55]. It is probable that only in the group of responders, because of differences in network connectivity and interactions with other neuromodulators, the VNS-induced activation of the LC-NE system results in a stronger inhibition and network reorganization that causes the antiepileptic effect.…”

“…Second, the vagus nerve has widespread projections to nuclei in the brainstem and to all cortical regions, as well as to the thalamus, hippocampus, and amygdala, where they modulate the activity of target cells and networks [1,2]. In addition, there are strong reciprocal connections between the different neuromodulatory systems (noradrenaline, dopamine, serotonin, and acetylcholine), which makes it very hard to delineate the role of one single system [18]. Consequently, the LC-NE system does not act alone, but interacts with other modulatory neurotransmitter pathways that also play an important contributive role in the antiepileptic effect of VNS.…”

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

“…This can be explained by the direct relationship of the FA to the axonal/microscopic organization within a voxel. FA in the basal forebrain tissue reflects cell bodies and axons, innervating axons of posterior brain regions such as the pons, as well as axons from the locus coeruleus which also pass through the basal forebrain en route to the cortex (Sara, 2009). In this tissue, a proportion of the axons, including cholinergic axons, are crossing over other axons.…”

Learning, the P3, and the Locus Coeruleus-Norepinephrine System

“…Recent research has suggested that the neuromodulatory brainstem nucleus locus coeruleus (LC) is critical for the regulation of cognitive performance Kehagia, Murray, & Robbins, 2010;Sara, 2009;Yu & Dayan, 2005). The LC exhibits a strong phasic increase in activity during the processing of motivationally relevant stimuli, leading to the release of the neuromodulatory neurotransmitter norepinephrine (NE) in the hippocampus, neocortex, and many other projection areas.…”