An in vivo assay of synaptic function mediating human cognition
Open accessAbstract
The contribution of dopamine to working memory has been studied extensively [1-3]. Here, we exploited its well characterized effects [1-3] to validate a novel human in vivo assay of ongoing synaptic [4, 5] processing. We obtained magnetoencephalographic (MEG) measurements from subjects performing a working memory (WM) task during a within-subject, placebo-controlled, pharmacological (dopaminergic) challenge. By applying dynamic causal modeling (DCM), a Bayesian technique for neuronal system identification [6], to MEG signals from prefrontal cortex, we demonstrate that it is possible to infer synaptic signaling by specific ion channels in behaving humans. Dopamine-induced enhancement of WM performance was accompanied by significant changes in MEG signal power, and a DCM assay disclosed related changes in synaptic signaling. By estimating the contribution of ionotropic receptors (AMPA, NMDA, and GABA(A)) to the observed spectral response, we demonstrate changes in their function commensurate with the synaptic effects of dopamine. The validity of our model is reinforced by a striking quantitative effect on NMDA and AMPA receptor signaling that predicted behavioral improvement over subjects. Our results provide a proof-of-principle demonstration of a novel framework for inferring, noninvasively, neuromodulatory influences on ion channel signaling via specific ionotropic receptors, providing a window on the hidden synaptic events mediating discrete psychological processes in humans.
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Validation studies in humans and animals show that DCM for EEG can capture short-term changes in synaptic efficacy, such as neuromodulation of glutamatergic receptor conductances, and distinguish different types of synaptic plasticity in cortical microcircuits.
“Validation studies in humans and animals have shown that DCM for EEG is capable of capturing short-term changes in synaptic efficacy, such as neuromodulation of glutamatergic receptor conductances, and distinguish different types of synaptic plasticity in cortical microcircuits (66, 132, 138–140)”
From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [66]
Boosting dopaminergic function enhances psychological and electrophysiological signatures of maintenance processes.
“while boosting dopaminergic function enhances psychological and electrophysiological signatures of such maintenance processes (Moran et al., 2011).”
From Goals and Habits in the Brain (2013) · cites this paper as Moran et al., 2011
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Shaw, A. D., Moran, R., Muthukumaraswamy, S. D., Brealy, J., Linden, D. E. J., Friston, K. J., & Singh, K. D. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.08.034 · Cited by 48 · see citing works
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Computational modelling of movement-related beta-oscillatory dynamics in human motor cortex
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Model selection and gobbledygook: Response to Lohmann et al.
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Cross-Frequency Power Coupling Between Hierarchically Organized Face-Selective Areas
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Self-citation
- Authors
- Moran, R. J., Symmonds, M., Stephan, K. E., Friston, K. J., & Dolan, R. J.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Moran, Rosalyn J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 21
- Issue
- 15
- Pages
- 1320-1325
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC3153654
- OpenAlex
- W2099907163
- Cited by
- 137
- References
- 46
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 9 · 2016: 15 · 2015: 17 · 2014: 17 · 2013: 17 · 2012: 6
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Explore Bristol Research (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (088130)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dopamine, working memory, synaptic signaling, ligand-gated ion channels, AMPA receptors, NMDA receptor, GABAA receptor, prefrontal cortex, dynamic causal modeling, magnetoencephalography, pharmacological challenge, neuromodulation
- MeSH terms
- Cognition, Dopamine, Humans, Memory, Synapses, Signal Transduction
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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