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Neuromodulation in circuits of aversive emotional learning

A Publisher Correction to this article was published on 11 October 2019

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Abstract

Emotional learning and memory are functionally and dysfunctionally regulated by the neuromodulatory state of the brain. While the role of excitatory and inhibitory neural circuits mediating emotional learning and its control have been the focus of much research, we are only now beginning to understand the more diffuse role of neuromodulation in these processes. Recent experimental studies of the acetylcholine, noradrenaline and dopamine systems in fear learning and extinction of fear responding provide surprising answers to key questions in neuromodulation. One area of research has revealed how modular organization, coupled with context-dependent coding modes, allows for flexible brain-wide or targeted neuromodulation. Other work has shown how these neuromodulators act in downstream targets to enhance signal-to-noise ratios and gain, as well as to bind distributed circuits through neuronal oscillations. These studies elucidate how different neuromodulatory systems regulate aversive emotional processing and reveal fundamental principles of neuromodulatory function.

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Fig. 1: Neuromodulatory projections overlap at their target sites.
Fig. 2: Basal forebrain connectivity with the aversive emotional learning network.
Fig. 3: Acetylcholine affects emotional learning via nicotinic and muscarinic receptors that enhance signal-to-noise ratios across regions.
Fig. 4: Context-dependent control of fear learning and extinction by the LC.
Fig. 5: Potential network architecture for state-dependent modular coding in LC.
Fig. 6: Projection-specific dopaminergic regulation of fear learning and extinction.

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  • 11 October 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

J.P.J. is supported by funding from the Japan Society for the Promotion of Science (KAKENHI, 19H05234). E.L. is supported by funding from the National Institute of Mental Health (R21MH114182).

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Likhtik, E., Johansen, J.P. Neuromodulation in circuits of aversive emotional learning. Nat Neurosci 22, 1586–1597 (2019). https://doi.org/10.1038/s41593-019-0503-3

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