{"id":10273,"date":"2016-10-21T06:59:49","date_gmt":"2016-10-21T06:59:49","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=10273"},"modified":"2016-10-21T06:59:49","modified_gmt":"2016-10-21T06:59:49","slug":"mapping-serotonin-dynamics-in-the-living-brain","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/mapping-serotonin-dynamics-in-the-living-brain\/","title":{"rendered":"Mapping serotonin dynamics in the living brain"},"content":{"rendered":"

Imaging technique that creates 3-D video of serotonin transport could aid antidepressant development.\u00a0<\/strong><\/em><\/p>\n

\"Molecular<\/a>
Molecular fMRI data showing signal changes from serotonin sensors in the absence (left) and presence (right) of the antidepressant Prozac, with each square denoting an individual brain voxel. Red squares indicate the signal has increased, as more serotonin is absorbed into neurons; blue squares indicate the signal has decreased, as less serotonin is absorbed into neurons. Dotted and solid lines graphed in each square show how the signal changes over time. The swirling black lines indicate features of the brain. A computer model uses this data to estimate neurotransmitter reuptake across the brain.
Courtesy of the researchers<\/figcaption><\/figure>\n

CAMBRIDGE, Mass<\/strong>. —\u00a0Serotonin is a neurotransmitter that\u2019s partly responsible for feelings of happiness and for mood regulation in humans. This makes it a common target for antidepressants, which block serotonin from being reabsorbed by neurons after it has dispatched its signal, so more of it stays floating around the brain.<\/p>\n

Now MIT researchers have developed an imaging technique that, for the first time, enables three-dimensional mapping of serotonin as it\u2019s reabsorbed into neurons, across multiple regions of the living brain. This technique, the researchers say, gives an unprecedented view of serotonin dynamics, and could be a powerful tool for the research and development of antidepressants.<\/p>\n

\u201cUntil now, it was not possible to look at how neurotransmitters are transported into cells across large regions of the brain,\u201d says Aviad Hai, a postdoc in the Department of Biological Engineering and first author of a\u00a0paper<\/a>\u00a0describing the technique in today\u2019s issue of\u00a0Neuron<\/em>. \u201cIt\u2019s the first time you can see the inhibitors of serotonin reuptake, like antidepressants, working in different parts of the brain, and you can use this information to analyze all sorts of antidepressant drugs, discover new ones, and see how those drugs affect the serotonin system across the brain.\u201d<\/p>\n

The paper\u2019s other authors are Alan Jasanoff, a professor of biological engineering; and three other researchers in Jasanoff\u2019s lab: Lili X. Cai, Taekwan Lee, and Victor S. Lelyveld.<\/p>\n

Measuring reuptake<\/strong><\/p>\n

Many antidepressants that target serotonin work by blocking serotonin transporters that reabsorb the neurotransmitter into a neuron, so it can be reused after it has sent a chemical signal. Aptly called \u201cselective serotonin reuptake inhibitors\u201d (SSRIs), these drugs increase levels of serotonin in the brain, alleviating feelings of anxiety and depression caused by low levels of the neurotransmitter.<\/p>\n

[pullquote]In the new system, a mathematical model uses the fMRI signal data to construct a 3-D map that consists of more than 1,000 voxels (pixels in three dimensions), with each voxel representing a single point of measurement of serotonin reuptake.[\/pullquote]<\/p>\n

Researchers most commonly study the effect of antidepressants using a technique known as microdialysis, in which they insert a probe into the brain to take tiny chemical samples from the tissue. But this method is time-consuming and limited in scope, as it allows them to study only a single location at a time.<\/p>\n

For the new imaging technique, the researchers engineered a protein to act as a sensor that latches onto serotonin and detaches at the moment of reuptake. The sensor is injected, along with serotonin, and emits a signal that can be read by functional magnetic resonance imaging (fMRI). The trick is that the sensor remains off \u2014 emitting a low signal \u2014 when bound to serotonin, and turns on \u2014 creating a much brighter signal \u2014 when serotonin is removed.<\/p>\n

In the new system, a mathematical model uses the fMRI signal data to construct a 3-D map that consists of more than 1,000 voxels (pixels in three dimensions), with each voxel representing a single point of measurement of serotonin reuptake. Based on the signal strength at each point, the model calculates the amount of serotonin that gets absorbed, in the presence and absence of SSRIs.<\/p>\n

\u201cBasically, what we\u2019ve seen in this work is a method for measuring how much of a neurotransmitter is being [absorbed], and how that amount, or rate, is affected by different drugs \u2026 in a highly parallel fashion across much of the brain,\u201d Jasanoff says. That information could be very valuable for testing drug efficacy, he says.<\/p>\n

Mapping antidepressant dynamics<\/strong><\/p>\n

To validate the sensor, the researchers successfully measured the expected effect of the SSRI fluoxetine, commonly called Prozac, on serotonin transporters in six subregions of a brain area known as the basal ganglia. These subregions are thought to play a role in motivation, reward, cognition, learning, emotion, and other functions and behaviors.<\/p>\n

In doing so, the researchers simultaneously recorded a stronger decrease of serotonin reuptake in response to Prozac among three of the subregions, while noting a very weak response in one other region. These results were, more or less, anticipated, Jasanoff says. \u201cBut now we\u2019re able to map that effect in three dimensions, across brain regions,\u201d he says, which could lead to advances in studying the effects of drugs on specific parts of the brain.<\/p>\n

But the researchers did uncover a surprising finding. While mapping the effects of a dopamine transport reuptake inhibitor \u2014 made to target only dopamine \u2014 they found the drug reduced serotonin reuptake, to an extent comparable to that of SSRIs, in three subregions, one of which is known for high dopamine transporter expression. Previous studies had indicated that dopamine transporter proteins can aid in low levels of serotonin reuptake, but the new findings show the effect is widespread in the living brain, Jasanoff says.<\/p>\n

This experiment provides further proof of a strong interplay between the serotonin and dopamine systems, and indicates that antidepressants may be less effective when targeting just one of the two neurotransmitters, Hai says. \u201cIt may not be sufficient to just block serotonin reuptake, because there\u2019s another system \u2014 dopamine \u2014 that plays a role in serotonin transport as well,\u201d he says. \u201cIt\u2019s almost proof that when you use antidepressants that \u2026 target both systems, it could be more effective.\u201d<\/p>\n

Next steps for the researchers are to explore different regions of the brain with this sensor, including the dorsal raphe, which produces most of the brain\u2019s serotonin. They\u2019re also making another nanoparticle-based sensor that is more sensitive than one used for this study.<\/p>\n

The research was funded by the National Institutes of Health, as well as fellowships from the Edmond and Lily Safra Center for Brain Sciences at the Hebrew University of Jerusalem, and the European Molecular Biology Organization.<\/p>\n","protected":false},"excerpt":{"rendered":"

Now MIT researchers have developed an imaging technique that, for the first time, enables three-dimensional mapping of serotonin as it\u2019s reabsorbed into neurons, across multiple regions of the living brain. This technique, the researchers say, gives an unprecedented view of serotonin dynamics, and could be a powerful tool for the research and development of antidepressants.<\/p>\n","protected":false},"author":6,"featured_media":10274,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[17],"tags":[],"class_list":["post-10273","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0-150x150.jpg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0-300x200.jpg",300,200,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",600,400,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",600,400,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",540,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",95,63,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",639,426,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",96,64,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/10\/MIT-Mapping-Serotonin_0.jpg",150,100,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/10273","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=10273"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/10273\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/10274"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=10273"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=10273"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=10273"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}