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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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.
The authors declare no competing interests
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Viral introduction of chemically engineered neurotransmitter receptors into neuronal membranes. These can be subsequently activated by pharmacological ligands that are specific to the receptor.
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.
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.
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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