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An in vivo assay of synaptic function mediating human cognition


Moran, Rosalyn J; Symmonds, Mkael; Stephan, K E; Friston, Karl J; Dolan, Raymond J (2011). An in vivo assay of synaptic function mediating human cognition. Current Biology, 21(15):1320-1325.

Abstract

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.

Abstract

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:03 Faculty of Economics > Department of Economics
Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > Neurochoice
08 University Research Priority Programs > Foundations of Human Social Behavior: Altruism and Egoism
Dewey Decimal Classification:570 Life sciences; biology
170 Ethics
330 Economics
Language:English
Date:2011
Deposited On:19 Aug 2011 12:33
Last Modified:03 Aug 2017 15:31
Publisher:Elsevier
ISSN:0960-9822
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.cub.2011.06.053
PubMed ID:21802302

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