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An in vivo assay of synaptic function mediating human cognition
Rosalyn J Moran1, Mkael Symmonds, Klaas E Stephan
1Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, UK. r.moran@fil.ion.ucl.ac.uk
Current Biology : CB
|August 2, 2011
Summary
Dopamine enhances working memory by altering synaptic signaling in the human brain. This study validates a new method to observe these non-invasive synaptic changes in real-time.
Area of Science:
- Neuroscience
- Cognitive Neuroscience
- Pharmacology
Background:
- Dopamine's role in working memory is well-established.
- Understanding synaptic processing in humans non-invasively is challenging.
Purpose of the Study:
- To validate a novel in vivo human assay for assessing synaptic processing.
- To investigate dopamine's effects on working memory and synaptic signaling.
Main Methods:
- Magnetoencephalography (MEG) was used to measure brain activity during a working memory task.
- Subjects underwent a placebo-controlled, dopaminergic pharmacological challenge.
- Dynamic Causal Modeling (DCM) was applied to MEG data from the prefrontal cortex.
Main Results:
- Dopamine administration enhanced working memory performance and altered MEG signal power.
- DCM analysis revealed corresponding changes in synaptic signaling, particularly in ionotropic receptors (AMPA, NMDA, GABA(A)).
- Changes in NMDA and AMPA receptor signaling quantitatively predicted behavioral improvements.
Conclusions:
- The study presents a proof-of-principle for a novel framework to non-invasively infer neuromodulatory influences on ion channel signaling.
- This method offers a window into synaptic events underlying cognitive processes in humans.
- The findings demonstrate the utility of DCM with MEG for studying brain function and drug effects.
