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Computational models link cellular mechanisms of neuromodulation to large-scale neural dynamics

Nature Neuroscience volume 24, pages 765–776 (2021)Cite this article

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Abstract

Decades of neurobiological research have disclosed the diverse manners in which the response properties of neurons are dynamically modulated to support adaptive cognitive functions. This neuromodulation is achieved through alterations in the biophysical properties of the neuron. However, changes in cognitive function do not arise directly from the modulation of individual neurons, but are mediated by population dynamics in mesoscopic neural ensembles. Understanding this multiscale mapping is an important but nontrivial issue. Here, we bridge these different levels of description by showing how computational models parametrically map classic neuromodulatory processes onto systems-level models of neural activity. The ensuing critical balance of systems-level activity supports perception and action, although our knowledge of this mapping remains incomplete. In this way, quantitative models that link microscale neuronal neuromodulation to systems-level brain function highlight gaps in knowledge and suggest new directions for integrating theoretical and experimental work.

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Fig. 1: Single-neuron gain.
Fig. 2: Sites of cellular neuromodulation.
Fig. 3: The ascending neuromodulatory arousal system.
Fig. 4: Neurobiological mechanisms for population gain.
Fig. 5: Macroscopic effects of neuromodulation.

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Acknowledgements

We thank C. Whyte and G. Wainstein for their thoughtful comments on our manuscript. We acknowledge funding from the NHMRC (GNT1118153 (M.B.), GNT1095227 (M.B.), GNT1193857 (J.M.S.)), The University of Sydney (J.M.S.) and the Portuguese Foundation for Science and Technology projects (UIDB/50026/2020, UIDP/50026/2020 and CEECIND/03325/2017 (J.C.)).

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  1. These authors contributed equally: James M. Shine, Eli J. Müller.

Authors and Affiliations

  1. Brain and Mind Center, The University of Sydney, Camperdown, New South Wales, Australia

    James M. Shine, Eli J. Müller & Brandon Munn

  2. Center for Complex Systems, The University of Sydney, Camperdown, New South Wales, Australia

    James M. Shine, Eli J. Müller & Brandon Munn

  3. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Joana Cabral

  4. Centre for Neuroimaging Science, King’s College, London, UK

    Rosalyn J. Moran

  5. School of Psychology, College of Engineering, Science and the Environment, University of Newcastle, Callaghan, New South Wales, Australia

    Michael Breakspear

  6. School of Medicine and Public Health, College of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia

    Michael Breakspear

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Shine, J.M., Müller, E.J., Munn, B. et al. Computational models link cellular mechanisms of neuromodulation to large-scale neural dynamics. Nat Neurosci 24, 765–776 (2021). https://doi.org/10.1038/s41593-021-00824-6

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