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The locus coeruleus and noradrenergic modulation of cognition

Nature Reviews Neuroscience volume 10, pages 211–223 (2009)Cite this article

Key Points

  • The noradrenergic nucleus locus coeruleus (LC) is a tiny cluster of cells located bilaterally in the pons just under the fourth ventricle. Despite its small size (it groups just 1,500 neurons on each side in the rat), it projects to the entire forebrain, brainstem and cerebellum.

  • The LC is part of what used to be known as the 'ascending reticular activating system', so it is not surprising that early theories of this system's function focused on vigilance and sleep–wake cycles.

  • Studies of the effects of noradrenaline at a cellular level reveal multiple actions, including effects on membrane potentials, cellular excitability, synaptic plasticity and the signal/noise ratio in sensory regions.

  • More recent studies have found that this system is implicated in many cognitive processes, including attention, learning, memory and decision making.

  • A large body of evidence has accumulated showing the LC noradrenaline system plays an important part in mediating behaviourally driven long-term potentiation and memory consolidation.

  • Functional-imaging studies suggest that this system is engaged in situations that require shifts in attention, perceptual rivalry and memory retrieval, supporting a general view that the LC promotes rapid neuronal-network reorganization in response to cognitive demand.

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.

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Figure 1: Anatomical connections that underlie interactions between the noradrenergic and dopaminergic systems.
Figure 2: Comparative anatomy of the distribution of noradrenergic and dopaminergic projections in the rat brain.
Figure 3: Noradrenergic signalling mechanisms for short- and long-lasting plasticity.
Figure 4: The influence of the LC on spike timing in two sensory systems.
Figure 5: The influence of the LC on stages of memory.
Figure 6: The human LC during memory retrieval.

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Acknowledgements

The author thanks S. Bouret, M. Segal and J.-P. Tassin for helpful comments on the manuscript and the Centre National de la Recherche Scientifique for ongoing support. Supported also by grants from ACI Neurosciences Integratives, Fondation de France (NRJ) and Volkswagenstiftung.

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Glossary

Volume transmission

Non-synaptic chemical signalling between neurons. It involves the diffusion into the extracellular space of a compound that has the ability to affect neurons several micrometres away during several hundred milliseconds.

Long-term potentiation

(LTP). A form of synaptic plasticity that results in a long-lasting increase in the strength of synaptic transmission.

Iontophoresis

The introduction of a substance into a cell by ion transfer, using electrodes to apply an electrical potential to the membrane.

Biphasic response

A neuronal response composed of an initial excitation, inhibition and then a second excitatory response.

Jitter

The trial-to-trial variability in the latency of a neuronal response to a specific stimulus.

Perforant pathway

The bundle of fibres that contains the axons of neurons that project from the entorhinal cortex to the hippocampus.

Hole board

A piece of apparatus used in rodent behavioural studies to measure exploratory activity and an animal's preference for or response to novelty.

Long-term depression

A form of synaptic plasticity that results in a long-lasting decrease in the strength of synaptic transmission.

Behaviourally relevant stimuli

Signals from the environment that elicit a response from an animal, usually approach or avoidance. These can be either primary rewards or punishments, such as food or predators, or stimuli that have been associated with primary reward or punishment.

Perceptual rivalry

The spontaneous switching from one subjective percept to another in the presence of ambiguous stimuli; it occurs in all sensory modalities.

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Sara, S. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10, 211–223 (2009). https://doi.org/10.1038/nrn2573

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