Molecular fMRI of Serotonin Transport
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Molecular fMRI with SI.pdf
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Author(s) • • • •
Hai, Aviad
Cai, Lili X.
Lee, Taekwan
Lelyveld, Victor S.
Jasanoff, Alan Pradip
Date Issued
October 2016
Journal
Neuron
Publisher
Elsevier/Cell Press
Citation
Hai, Aviad et al. “Molecular fMRI of Serotonin Transport.” Neuron 92, 4 (November 2016): 754–765 © 2016 Elsevier
Version
Author's final manuscript
Abstract
Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe. Application of this strategy to much of the striatum and surrounding areas reveals widespread nonsaturating serotonin removal with maximal rates in the lateral septum. The serotonin reuptake inhibitor fluoxetine selectively suppresses serotonin removal in septal subregions, whereas both fluoxetine and a dopamine transporter blocker depress reuptake in striatum. These results highlight promiscuous pharmacological influences on the serotonergic system and demonstrate the utility of molecular fMRI for characterization of neurochemical dynamics.
Keywords
antidepressant; reuptake transporter; SSRI; molecular imaging; serotonin; fMRI; magnetic resonance imaging; in vivo; striatum; dopamine
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Nuclear Science and Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2016.09.048