{"id":34336,"date":"2022-07-20T00:00:37","date_gmt":"2022-07-20T07:00:37","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=34336"},"modified":"2024-01-30T14:23:02","modified_gmt":"2024-01-30T22:23:02","slug":"making-a-memory-positive-or-negative","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/making-a-memory-positive-or-negative\/","title":{"rendered":"\u8ba9\u8bb0\u5fc6\u53d8\u5f97\u79ef\u6781\u6216\u6d88\u6781"},"content":{"rendered":"<p>LA JOLLA\u2014Researchers at the Salk Institute and colleagues have discovered the molecule in the brain responsible for associating good or bad feelings with a memory. Their discovery, published in <a href=\"https:\/\/www.nature.com\/articles\/s41586-022-04964-y\" rel=\"noopener\" target=\"_blank\"><em>Nature<\/em><\/a> on July 20, 2022, paves the way for a better understanding of why some people are more likely to retain negative emotions than positive ones\u2014as can occur with anxiety, depression or post-traumatic stress disorder (PTSD). <\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-12 col-md-push-0\"><div class=\"video-anchor\" id=\"video-uhnD9anrB64\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/uhnD9anrB64?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>\u201cWe\u2019ve basically gotten a handle on the fundamental biological process of how you can remember if something is good or bad,\u201d says senior author <a href=\"https:\/\/www.salk.edu\/zh\/scientist\/kay-tye\/\">\u51ef\u6cf0<\/a>, a professor in Salk\u2019s Systems Neurobiology Laboratory and a Howard Hughes Medical Institute Investigator. \u201cThis is something that\u2019s core to our experience of life, and the notion that it can boil down to a single molecule is incredibly exciting.\u201d<\/p>\n<p>For a human or animal to learn whether to avoid, or seek out, a particular experience again in the future, their brain must associate a positive or negative feeling, or \u201cvalence\u201d with that stimulus. The brain\u2019s ability to link these feelings with a memory is called \u201cvalence assignment.\u201d<\/p>\n<p>In 2016, Tye discovered that a group of neurons in the brain\u2019s basolateral amygdala (BLA) helps assign valence when mice are learning. One set of BLA neurons was activated with positive valence, as the animals learned to associate a tone with a sweet taste. A separate set of BLA neurons was activated with negative valence, as the animals learned to associate a different tone with a bitter taste.<\/p>\n<figure id=\"attachment_35311\"  class=\"wp-caption alignright\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"290\" class=\"img-responsive wp-image-35311 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-458x290.jpg\" alt=\"Expression of various genes and proteins (white, red, and green) in neurons amongst mouse brain cells (blue). \" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-458x290.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-300x190.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-1024x649.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-768x487.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-147x93.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-585x371.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-553x350.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-750x475.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-767x486.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-945x599.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr-400x254.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr.jpg 1248w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><\/a><figcaption class=\"wp-caption-text\">Expression of various genes and proteins (white, red, and green) in neurons amongst mouse brain cells (blue).<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/CRISPR_merge2_cropped-hr.jpg\">Click here<\/a> for a high-resolution image.<br \/>Credit: Salk Institute<\/figcaption><\/figure>\n<p>\u201cWe found these two pathways\u2014analogous to railroad tracks\u2014that were leading to positive and negative valence, but we still didn\u2019t know what signal was acting as the switch operator to direct which track should be used at any given time,\u201d says Tye, holder of the Wylie Vale Chair.<\/p>\n<p>In the new study, the researchers homed in on the importance of the signaling molecule neurotensin to these BLA neurons. They already knew that neurotensin is a neuropeptide produced by the cells associated with valence processing, but so are a few other neurotransmitters. So they used CRISPR gene editing approaches to selectively remove the gene for neurotensin from the cells\u2014the first time that CRISPR has been used to isolate specific neurotransmitter function.<\/p>\n<p>Without neurotensin signaling in the BLA, mice could no longer assign positive valence and didn\u2019t learn to associate the first tone with a positive stimulus. Interestingly, the absence of neurotensin did not block negative valence. The animals instead became even better at negative valence, having a stronger association between the second tone and a negative stimulus.<\/p>\n<p>The findings suggest that the brain\u2019s default state is to have a bias toward fear\u2014the neurons associated with negative valence are activated until neurotensin is released, switching on the neurons associated with positive valence. From an evolutionary perspective, Tye says, this makes sense because it helps people avoid potentially dangerous situations\u2014and it probably resonates with people who tend to find the worst in a situation.<\/p>\n<p>In further experiments, Tye and her team showed that high levels of neurotensin promoted reward learning and dampened negative valence, further supporting the idea that neurotensin is responsible for positive valence.<\/p>\n<figure id=\"attachment_34348\"  class=\"wp-caption alignleft\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"305\" class=\"img-responsive wp-image-34348 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-458x305.jpg\" alt=\"From left: Kay Tye and Hao Li\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-767x511.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-945x630.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-1250x833.jpg 1250w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2-400x267.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2.jpg 1500w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><\/a><figcaption class=\"wp-caption-text\">From left: Kay Tye and Hao Li<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/04\/Tye-Li-PR-20211215-551A2551-2.jpg\">Click here<\/a> for a high-resolution image.<br \/>Credit: Salk Institute<\/figcaption><\/figure>\n<p>\u201cWe can actually manipulate this switch to turn on positive or negative learning,\u201d says co-first author Hao Li, a postdoctoral fellow in the Tye Lab. \u201cUltimately, we\u2019d like to try to identify novel therapeutic targets for this pathway.\u201d<\/p>\n<p>The researchers still have questions about whether levels of neurotensin can be modulated in people\u2019s brains to treat anxiety or PTSD. They are also planning future studies to probe what other brain pathways and molecules are responsible for triggering the release of neurotensin.<\/p>\n<p>Other authors of the paper were Matilde Borio, Mackenzie Lemieux, Austin Coley, Avraham Libster, Aneesh Bal, Caroline Jia, Jasmin Revanna, Kanha Batra, Kyle Fischer, Laurel Keyes, Nancy Padilla-Coreano and Romy Wichmann of Salk; Praneeth Namburi, Jacob Olson, Anna Beyeler, Gwendolyn Calhoon, Natsuko Hitora-Imamura, Ada Felix-Ortiz, Ver\u00f3nica de la Fuente, Vanessa Barth, Hunter King, Ehsan Izadmehr, Cody Siciliano and Ila Fiete of MIT; Xin Jin, Sourav Choudhury, Xi Shi and Feng Zhang of the Broad Institute of MIT and Harvard; Huan Wang and Yulong Li of Peking University; and Kenneth McCullough and Kerry Ressler of Harvard Medical School.<\/p>\n<p>The work was supported by the JPB Foundation, PIIF, PNDRF, JFDP, Alfred P. Sloan Foundation, New York Stem Cell Foundation, Klingenstein Foundation, McKnight Foundation, Clayton Foundation, National Institutes of Health (R01-MH102441, RF1-AG047661, DP2-DK102256, DP1-AT009925, F32 MH115446-01 and K99 DA055111), the Brain and Behavior Research Foundation, MEXT (15K21744, 17H06043), the Uehara Memorial Foundation, Singleton, Leventhal and Whitaker fellowships, a fellowship from the Swiss National Science Foundation and a Fulbright scholarship.<\/p>","protected":false},"featured_media":35333,"template":"","faculty":[326],"disease-research":[458,161,124],"class_list":["post-34336","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-kay-tye","disease-research-anxiety","disease-research-depression","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Making a memory positive or negative - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/making-a-memory-positive-or-negative\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Making a memory positive or negative - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Researchers at the Salk Institute and colleagues have discovered the molecule in the brain responsible for associating good or bad feelings with a memory. 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Olson, Matilde Borio, Mackenzie E. Lemieux, Anna Beyeler, Gwendolyn G. Calhoon, Natsuko Hitora-Imamura, Austin A. Coley, Avraham Libster, Aneesh Bal, Xin Jin, Huan Wang, Caroline Jia, Sourav R. Choudhury, Xi Shi, Ada C. Felix-Ortiz, Ver\u00f3nica de la Fuente, Vanessa P. Barth, Hunter O. King, Ehsan M. Izadmehr, Jasmin S. Revanna, Kanha Batra, Kyle B. Fischer, Laurel R. Keyes, Nancy Padilla-Coreano, Cody A. Siciliano, Kenneth M. McCullough, Romy Wichmann, Kerry J. Ressler, Ila R. Fiete, Feng Zhang, Yulong Li and Kay M. 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