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Locus coeruleus: a new look at the blue spot

Nature Reviews Neuroscience volume 21, pages 644–659 (2020)Cite this article

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Abstract

The locus coeruleus (LC), or ‘blue spot’, is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the brain. This phylogenetically conserved nucleus has proved relatively intractable to full characterization, despite more than 60 years of concerted efforts by investigators. Recently, an array of powerful new neuroscience tools have provided unprecedented access to this elusive nucleus, revealing new levels of organization and function. We are currently at the threshold of major discoveries regarding how this tiny brainstem structure exerts such varied and significant influences over brain function and behaviour. All LC neurons receive inputs related to autonomic arousal, but distinct subpopulations of those neurons can encode specific cognitive processes, presumably through more specific inputs from the forebrain areas. This ability, combined with specific patterns of innervation of target areas and heterogeneity in receptor distributions, suggests that activation of the LC has more specific influences on target networks than had initially been imagined.

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Fig. 1: The blue spot: past discoveries and future horizons.
Fig. 2: Evolving views of the LC synaptic architecture and functional organization.
Fig. 3: GANE release creates local NA ‘hot spots’ and alters network processing: the network GANE model.

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Acknowledgements

Funding for the 3-day workshop that generated this Perspective was provided by a grant from the Albert and Elaine Borchard Foundation Center on International Education to G.R.P. and S.J.S.Research funding to D.M.-V.: German Research Foundation project no.: 316803389, SFB 1280/A04.

Author information

Authors and Affiliations

  1. UCLA, Integrative Biology and Physiology, Los Angeles, CA, USA

    Gina R. Poe

  2. 5312 Hampden Lane, Bethesda, MD, USA

    Stephen Foote

  3. Max Planck Institute for Biological Cybernetics, Physiology of Cognitive Processes, Tuebingen, Germany

    Oxana Eschenko

  4. Riken, Center for Brain Science, Saitama, Japan

    Joshua P. Johansen

  5. ICM, Institut du Cerveau et de la Moelle Epinière, Hôpital Pitié-Salpêtrière, Paris, France

    Sebastien Bouret

  6. Rutgers University, Brain Health Institute, Piscataway, NJ, USA

    Gary Aston-Jones

  7. Memorial University, Newfoundland, Psychology Department, St John’s, NL, Canada

    Carolyn W. Harley

  8. Ruhr University Bochum, Medical Faculty, Neurophysiology, Bochum, Germany

    Denise Manahan-Vaughan

  9. Emory University, Human Genetics, Atlanta, GA, USA

    David Weinshenker

  10. NIH, National Institute on Drug Abuse, Bethesda, MD, USA

    Rita Valentino

  11. University Wisconsin-Madison, Psychology, Madison, WI, USA

    Craig Berridge

  12. Rowan University School of Osteopathic Medicine, Cell Biology and Neuroscience, Stratford, NJ, USA

    Daniel J. Chandler & Barry Waterhouse

  13. Collège de France, Centre for Interdisciplinary Research in Biology, Paris, France

    Susan J. Sara

  14. New York University Medical School, Child and Adolescent Psychiatry, New York, NY, USA

    Susan J. Sara

Authors
  1. Gina R. Poe
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  2. Stephen Foote
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  3. Oxana Eschenko
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  4. Joshua P. Johansen
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  5. Sebastien Bouret
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  6. Gary Aston-Jones
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  7. Carolyn W. Harley
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  8. Denise Manahan-Vaughan
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  9. David Weinshenker
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  10. Rita Valentino
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  11. Craig Berridge
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  12. Daniel J. Chandler
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  13. Barry Waterhouse
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  14. Susan J. Sara
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Contributions

All authors contributed equally to the manuscript.

Corresponding author

Correspondence to Susan J. Sara.

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The authors declare no competing interests

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Nature Reviews Neuroscience thanks M. Mather and the other anonymous reviewers for their contribution to the peer review of this work.

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Glossary

Chemogenetics

Viral introduction of chemically engineered neurotransmitter receptors into neuronal membranes. These can be subsequently activated by pharmacological ligands that are specific to the receptor.

Co-transmitters

Neuromodulators released from a neuron along with a primary neurotransmitter.

Fast-scan voltammetry

Voltammetry examines fluctuations in current that are driven by variations in voltage/potential. In cyclic voltammetry, after the desired potential is reached, the potential is ramped in the opposite direction to return to the initial potential (time-locked voltage oscillations), causing the substance of interest to be oxidized and reduced in predetermined cycles. The concentration of the substance can be calculated by generating a calibration curve of current against concentration, allowing the relative concentration to be calculated within milliseconds, and thus the real-time detection of neurotransmitter concentration.

Fear extinction

Learning that a context or cue that was associated with an aversive event no longer predicts that event, and thus the fear response to that context or cue is no longer expressed.

Frequency tuning

In the auditory cortex, individual neurons exhibit a specific response pattern based on the sound frequency applied. Delivery of a set of different sound frequencies determines the frequency tuning of the neuron.

Optogenetics

Analysis via the viral introduction of light-sensitive channels or ion pumps into neuronal membranes, which subsequently can be driven by the external application of a specific light wavelength.

RNAi

RNA interference, which comprises the inhibition of gene expression or translation by silencing the target mRNA.

Terminal fields

Neural areas targeted by axonal projections.

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Poe, G.R., Foote, S., Eschenko, O. et al. Locus coeruleus: a new look at the blue spot. Nat Rev Neurosci 21, 644–659 (2020). https://doi.org/10.1038/s41583-020-0360-9

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