Molecular fMRI of Serotonin Transport
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-lev...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier/Cell Press
2017
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| Online Access: | http://hdl.handle.net/1721.1/112294 https://orcid.org/0000-0002-4556-3048 https://orcid.org/0000-0002-3890-0288 https://orcid.org/0000-0002-2834-6359 |
| _version_ | 1811081090710896640 |
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| author | Hai, Aviad Cai, Lili X. Lee, Taekwan Lelyveld, Victor S. Jasanoff, Alan Pradip |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Hai, Aviad Cai, Lili X. Lee, Taekwan Lelyveld, Victor S. Jasanoff, Alan Pradip |
| author_sort | Hai, Aviad |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T11:41:28Z |
| format | Article |
| id | mit-1721.1/112294 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:41:28Z |
| publishDate | 2017 |
| publisher | Elsevier/Cell Press |
| record_format | dspace |
| spelling | mit-1721.1/1122942022-09-27T21:16:31Z Molecular fMRI of Serotonin Transport Hai, Aviad Cai, Lili X. Lee, Taekwan Lelyveld, Victor S. Jasanoff, Alan Pradip 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 Jasanoff, Alan Hai, Aviad Cai, Lili X. Lee, Taekwan Lelyveld, Victor S. Jasanoff, Alan Pradip 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 National Institutes of Health (U.S.) (Grant R01 DA028299) National Institutes of Health (U.S.) (Grant R01 DA038642) National Institutes of Health (U.S.) (Grant R01 NS076462) 2017-11-27T19:31:36Z 2017-11-27T19:31:36Z 2016-10 2016-06 Article http://purl.org/eprint/type/JournalArticle 0896-6273 1097-4199 http://hdl.handle.net/1721.1/112294 Hai, Aviad et al. “Molecular fMRI of Serotonin Transport.” Neuron 92, 4 (November 2016): 754–765 © 2016 Elsevier https://orcid.org/0000-0002-4556-3048 https://orcid.org/0000-0002-3890-0288 https://orcid.org/0000-0002-2834-6359 en_US http://dx.doi.org/10.1016/j.neuron.2016.09.048 Neuron Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier/Cell Press Prof. Jasanoff via Howard Silver |
| spellingShingle | Hai, Aviad Cai, Lili X. Lee, Taekwan Lelyveld, Victor S. Jasanoff, Alan Pradip Molecular fMRI of Serotonin Transport |
| title | Molecular fMRI of Serotonin Transport |
| title_full | Molecular fMRI of Serotonin Transport |
| title_fullStr | Molecular fMRI of Serotonin Transport |
| title_full_unstemmed | Molecular fMRI of Serotonin Transport |
| title_short | Molecular fMRI of Serotonin Transport |
| title_sort | molecular fmri of serotonin transport |
| url | http://hdl.handle.net/1721.1/112294 https://orcid.org/0000-0002-4556-3048 https://orcid.org/0000-0002-3890-0288 https://orcid.org/0000-0002-2834-6359 |
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