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Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation
The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 second...
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Published in: | Science (American Association for the Advancement of Science) 2017-05, Vol.356 (6340), p.853-859 |
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description | The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons. |
doi_str_mv | 10.1126/science.aam7100 |
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We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons.</description><identifier>ISSN: 0036-8075</identifier><identifier>ISSN: 1095-9203</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aam7100</identifier><identifier>PMID: 28546212</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Ablation ; Animals ; Axons ; Axons - metabolism ; Body weight ; Body weight gain ; Brain ; Bulimia ; Bulimia - physiopathology ; Deprivation ; Diet, High-Fat ; Dietary restrictions ; Eating ; Eating - physiology ; Eating behavior ; Eating disorders ; Eating Habits ; Feeding ; Feeding behavior ; Feeding Behavior - physiology ; Food ; Food Deprivation ; Food intake ; Food Preferences - physiology ; Foods ; GABAergic Neurons - physiology ; Gain ; Ghrelin ; Ghrelin - metabolism ; Glutamic Acid - metabolism ; Hunger ; Hunger - physiology ; Mice ; Neurons ; Nuclei ; Obesity ; Optogenetics ; Philosophy ; Post-Synaptic Density - metabolism ; Presynaptic Terminals - metabolism ; Projection ; Rodents ; Stimulation ; Thalamus ; Thalamus - cytology ; Thalamus - physiology ; Weight Gain - physiology ; Weight reduction ; Zona incerta ; Zona Incerta - cytology ; Zona Incerta - physiology ; γ-Aminobutyric acid</subject><ispartof>Science (American Association for the Advancement of Science), 2017-05, Vol.356 (6340), p.853-859</ispartof><rights>Copyright © 2017 by the American Association for the Advancement of Science</rights><rights>Copyright © 2017, American Association for the Advancement of Science.</rights><rights>Copyright © 2017, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c575t-900bc4a672fdf3b398224ae7bdaa7d8d48a40a1894afd499b254767673593e9f3</citedby><cites>FETCH-LOGICAL-c575t-900bc4a672fdf3b398224ae7bdaa7d8d48a40a1894afd499b254767673593e9f3</cites><orcidid>0000-0002-5707-193X ; 0000-0002-4959-1660</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26399097$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26399097$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,885,2884,2885,27924,27925,58238,58471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28546212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiaobing</creatorcontrib><creatorcontrib>van den Pol, Anthony N.</creatorcontrib><title>Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons.</description><subject>Ablation</subject><subject>Animals</subject><subject>Axons</subject><subject>Axons - metabolism</subject><subject>Body weight</subject><subject>Body weight gain</subject><subject>Brain</subject><subject>Bulimia</subject><subject>Bulimia - physiopathology</subject><subject>Deprivation</subject><subject>Diet, High-Fat</subject><subject>Dietary restrictions</subject><subject>Eating</subject><subject>Eating - physiology</subject><subject>Eating behavior</subject><subject>Eating disorders</subject><subject>Eating Habits</subject><subject>Feeding</subject><subject>Feeding behavior</subject><subject>Feeding Behavior - physiology</subject><subject>Food</subject><subject>Food Deprivation</subject><subject>Food intake</subject><subject>Food Preferences - physiology</subject><subject>Foods</subject><subject>GABAergic Neurons - physiology</subject><subject>Gain</subject><subject>Ghrelin</subject><subject>Ghrelin - metabolism</subject><subject>Glutamic Acid - metabolism</subject><subject>Hunger</subject><subject>Hunger - physiology</subject><subject>Mice</subject><subject>Neurons</subject><subject>Nuclei</subject><subject>Obesity</subject><subject>Optogenetics</subject><subject>Philosophy</subject><subject>Post-Synaptic Density - metabolism</subject><subject>Presynaptic Terminals - metabolism</subject><subject>Projection</subject><subject>Rodents</subject><subject>Stimulation</subject><subject>Thalamus</subject><subject>Thalamus - cytology</subject><subject>Thalamus - physiology</subject><subject>Weight Gain - physiology</subject><subject>Weight reduction</subject><subject>Zona incerta</subject><subject>Zona Incerta - cytology</subject><subject>Zona Incerta - physiology</subject><subject>γ-Aminobutyric acid</subject><issn>0036-8075</issn><issn>1095-9203</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqNks1vFCEYxonR2LV69qQh8eJlWr4ZLibbRqtJExOjFy_knYHZss7CCjNr1r9eml3rx6nhQOD58cD78iD0nJIzSpk6L33wsfdnABtNCXmAFpQY2RhG-EO0IISrpiVanqAnpawJqZrhj9EJa6VQjLIF-voJtsHhLsSVb8bwzWMPU11giHU3uT3-4cPqZsIrCBG7HHY-4m6Pf6YIONSr8wT4anmxxNHPOUUM_RR21SLFp-jRAGPxz47zKfry7u3ny_fN9cerD5fL66aXWk6NIaTrBSjNBjfwjpuWMQFedw5Au9aJFgQB2hoBgxPGdEwKrergtRZvBn6K3hx8t3O38a73ccow2m0OG8h7myDYf5UYbuwq7axShEkuq8Hro0FO32dfJrsJpffjCNGnuVhqqORMMmHugRIlpGJc3wflVBpJ2oq--g9dpznH2rRbqr6xGtJKnR-oPqdSsh_uSqTE3qbBHtNgj2moJ17-3Zk7_vf3V-DFAViXKeU_uuLGEKP5LyFCu1A</recordid><startdate>20170526</startdate><enddate>20170526</enddate><creator>Zhang, Xiaobing</creator><creator>van den Pol, Anthony N.</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5707-193X</orcidid><orcidid>https://orcid.org/0000-0002-4959-1660</orcidid></search><sort><creationdate>20170526</creationdate><title>Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation</title><author>Zhang, Xiaobing ; van den Pol, Anthony N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c575t-900bc4a672fdf3b398224ae7bdaa7d8d48a40a1894afd499b254767673593e9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Ablation</topic><topic>Animals</topic><topic>Axons</topic><topic>Axons - metabolism</topic><topic>Body weight</topic><topic>Body weight gain</topic><topic>Brain</topic><topic>Bulimia</topic><topic>Bulimia - physiopathology</topic><topic>Deprivation</topic><topic>Diet, High-Fat</topic><topic>Dietary restrictions</topic><topic>Eating</topic><topic>Eating - physiology</topic><topic>Eating behavior</topic><topic>Eating disorders</topic><topic>Eating Habits</topic><topic>Feeding</topic><topic>Feeding behavior</topic><topic>Feeding Behavior - physiology</topic><topic>Food</topic><topic>Food Deprivation</topic><topic>Food intake</topic><topic>Food Preferences - physiology</topic><topic>Foods</topic><topic>GABAergic Neurons - physiology</topic><topic>Gain</topic><topic>Ghrelin</topic><topic>Ghrelin - metabolism</topic><topic>Glutamic Acid - metabolism</topic><topic>Hunger</topic><topic>Hunger - physiology</topic><topic>Mice</topic><topic>Neurons</topic><topic>Nuclei</topic><topic>Obesity</topic><topic>Optogenetics</topic><topic>Philosophy</topic><topic>Post-Synaptic Density - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiaobing</au><au>van den Pol, Anthony N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2017-05-26</date><risdate>2017</risdate><volume>356</volume><issue>6340</issue><spage>853</spage><epage>859</epage><pages>853-859</pages><issn>0036-8075</issn><issn>1095-9203</issn><eissn>1095-9203</eissn><abstract>The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) γ-aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>28546212</pmid><doi>10.1126/science.aam7100</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-5707-193X</orcidid><orcidid>https://orcid.org/0000-0002-4959-1660</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Ablation Animals Axons Axons - metabolism Body weight Body weight gain Brain Bulimia Bulimia - physiopathology Deprivation Diet, High-Fat Dietary restrictions Eating Eating - physiology Eating behavior Eating disorders Eating Habits Feeding Feeding behavior Feeding Behavior - physiology Food Food Deprivation Food intake Food Preferences - physiology Foods GABAergic Neurons - physiology Gain Ghrelin Ghrelin - metabolism Glutamic Acid - metabolism Hunger Hunger - physiology Mice Neurons Nuclei Obesity Optogenetics Philosophy Post-Synaptic Density - metabolism Presynaptic Terminals - metabolism Projection Rodents Stimulation Thalamus Thalamus - cytology Thalamus - physiology Weight Gain - physiology Weight reduction Zona incerta Zona Incerta - cytology Zona Incerta - physiology γ-Aminobutyric acid |
title | Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation |
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