{"id":50243,"date":"2024-07-22T08:40:44","date_gmt":"2024-07-22T15:40:44","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&p=50243"},"modified":"2024-07-25T11:01:46","modified_gmt":"2024-07-25T18:01:46","slug":"new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/","title":{"rendered":"Nuevas herramientas revelan que son los neurop\u00e9ptidos, y no los neurotransmisores r\u00e1pidos, los que codifican el peligro en el cerebro"},"content":{"rendered":"

LA JOLLA\u2014In the split second as you accidentally touch the hot handle of a cast iron skillet, pain and a sense of danger rush in. Sensory signals travel from the pain receptors in your finger, up through your spinal cord, and into your brainstem. Once there, a special group of neurons relays those pain signals to a higher brain area called the amygdala, where they trigger your emotional fear response and help you remember to avoid hot skillets in the future. \r\n<\/p>\r\n

\"From<\/a>
From left: Sung Han and Dong-Il Kim.
Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\r\n

\r\nThis process of translating pain into a threat memory occurs so quickly that scientists thought it must be mediated by fast-acting neurotransmitters. But when Salk researchers investigated the role of larger, slower-acting molecules called neuropeptides, they discovered these were the primary messengers in this fear circuit.\r\n<\/p>

\r\nNeuropeptides are known to play an important role in brain communication, but the details have been unclear because scientists didn\u2019t have the proper tools to study them in behaving animals. To determine the role of neuropeptides in this circuit, the Salk team created two new tools that finally allow scientists to observe and manipulate neuropeptide release in the brains of live mice. \r\n<\/p>

\r\nThe new study, published in C\u00e9lula<\/a><\/em> on July 22, 2024, revealed that the danger circuit relies on neuropeptides as its primary messengers, not fast neurotransmitters, and more than one neuropeptide is involved in the process. Their findings could lead to the development of more effective painkillers or new treatments for fear-related conditions like anxiety and PTSD (post-traumatic stress disorder).\r\n<\/p>

\r\n\u201cThere is so much we have left to uncover about neuropeptides, but thankfully at Salk, we have the legacy of Nobel Prize winner Roger Guillemin<\/a>\u2019s work to highlight their importance and encourage our discovery,\u201d says senior author Sung Han<\/a>, associate professor and Pioneer Fund Development Chair at Salk. \u201cTo do this, we created two genetically encoded tools for monitoring and silencing neuropeptide release from nerve endings. We believe these new tools will significantly advance the field of neuropeptide research, and our discovery of their role in fear processing is really just the beginning.\u201d\r\n<\/p>

\r\nTo process and react to things in our environment, information must travel throughout our body and brain. These signals are sent and received by neurons, which form organized circuits that guide information where it needs to go. Neurons communicate with each other by sending and receiving molecules like neurotransmitters and neuropeptides.\r\n<\/p>

\"Two<\/a>
Two images of nerve endings in the amygdala (where fear signals are received and interpreted). On the left, there are no labels and two distinct vesicles in the nerve endings can be seen. On the right, neuropeptide sensors are labeled in dark color, and they can be seen inside large dense core vesicles.
Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>

\r\nNeuropeptides are generally accepted as neuromodulators that help and modulate the action of main neurotransmitters. However, early pioneers like Roger Guillemin proposed that neuropeptides can act as main transmitters themselves. This concept has not been rigorously tested due to the lack of tools for visualizing and manipulating their release in behaving animals. The Salk team set out to explore neuropeptides with the goal of developing new tools to better understand their role in brain circuits.\r\n<\/p>

\r\nTo specifically target neuropeptides, Han\u2019s team took advantage of one of their unique characteristics\u2014while typical neurotransmitters are packaged in small spheres called synaptic vesicles, neuropeptides are packaged in large dense core vesicles<\/em>. By engineering biochemical tools to target these large vesicles, they created neuropeptide sensor and silencer tools. The sensor tags large dense core vesicles with proteins that glow when they are released from the nerve ending, allowing the researchers to watch neuropeptide release in live time. The silencer specifically degrades neuropeptides within large dense core vesicles, revealing what happens in the brain when neuropeptides are absent.\r\n<\/p>

\r\n\"We have created a novel way to trace neuropeptide travel and function in the brains of living animals,\u201d says Dong-Il Kim, first author of the study and postdoctoral researcher in Han\u2019s lab. \u201cThese tools will help further our understanding of the brain\u2019s neuropeptide circuits and enable neuroscientists to explore questions that were previously difficult to address.\u201d\r\n<\/p>

\r\nUsing their newly developed neuropeptide sensor and silencer, together with existing sensor and silencer tools for glutamate (the brain\u2019s most abundant neurotransmitter), the researchers looked at how neuropeptides and glutamate behaved in live mice as they experienced a mild stimulus\u2014just enough to stimulate the fear circuit. They found that neuropeptides, but not glutamate, were released during the stimulus. What\u2019s more, silencing neuropeptide release reduced fear behaviors in the mice, but silencing glutamate had no effect.\r\n<\/p>

\r\nTo Han\u2019s surprise and delight, this brainstem fear circuit relied on neuropeptides as its primary messenger molecules rather than glutamate. Furthermore, their findings support their ongoing investigation into PACAP\u2014a neuropeptide that modulates panic disorder<\/a>.\r\n<\/p>

\r\n\u201cThese new tools and discoveries are an important step toward better neurological drug development,\u201d says Han. \u201cWe found that multiple neuropeptides are packaged together in a single vesicle and released all at once by a painful stimulus to function in this fear circuit, which made us think, \u2018This<\/em> might be why some drugs that target only one neuropeptide are failing in clinical trials.\u2019 With this new information, we can provide insights to develop new drugs that target multiple neuropeptide receptors at once, which may serve as better painkillers or help treat fear-related disorders like PTSD.\u201d \r\n<\/p>

\r\nEquipped with their new neuropeptide toolbox, the team will soon begin to explore other brain circuits and processes. Future insights into neuropeptide signaling in other areas of the brain, as well as the newfound understanding that targeting multiple neuropeptides at once is necessary, should inspire the development of more effective drugs to treat diverse neurological disorders. \r\n<\/p>

\r\nOther authors include Seahyung Park, Mao Ye, Sukjae Kang, Jinho Jhang, Joan Vaughan, and Alan Saghatelian of Salk; Sekun Park, Jane Chen, Avery Hunker, Larry Zweifel, and Richard Palmiter of University of Washington; and Kathleen Caron of University of North Carolina at Chapel Hill.\r\n<\/p>

\r\nThe work was supported by the National Institutes of Health (NIMH 5R01MH116203, NINDS 1RF1NS128680) and a Salk Institute Innovation Grant<\/a>.\r\n<\/p>","protected":false},"featured_media":50252,"template":"","faculty":[294],"disease-research":[458,124,465],"class_list":["post-50243","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-sung-han","disease-research-anxiety","disease-research-neuroscience-and-neurological-disorders","disease-research-pain"],"acf":[],"yoast_head":"\nNew tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain - 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\/es\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014In the split second as you accidentally touch the hot handle of a cast iron skillet, pain and a sense of danger rush in. Sensory signals travel from the pain receptors in your finger, up through your spinal cord, and into your brainstem. Once there, a special group of neurons relays those pain signals to a higher brain area called the amygdala, where they trigger your emotional fear response and help you remember to avoid hot skillets in the future.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/es\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2024-07-25T18:01:46+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/07\/image-sq.png\" \/>\n\t<meta property=\"og:image:width\" content=\"767\" \/>\n\t<meta property=\"og:image:height\" content=\"767\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/\",\"name\":\"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2024\\\/07\\\/image-sq.png\",\"datePublished\":\"2024-07-22T15:40:44+00:00\",\"dateModified\":\"2024-07-25T18:01:46+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/#breadcrumb\"},\"inLanguage\":\"es-MX\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"es-MX\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2024\\\/07\\\/image-sq.png\",\"contentUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2024\\\/07\\\/image-sq.png\",\"width\":767,\"height\":767},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"es-MX\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"es-MX\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/es\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/","og_locale":"es_MX","og_type":"article","og_title":"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain - Salk Institute for Biological Studies","og_description":"LA JOLLA\u2014In the split second as you accidentally touch the hot handle of a cast iron skillet, pain and a sense of danger rush in. Sensory signals travel from the pain receptors in your finger, up through your spinal cord, and into your brainstem. Once there, a special group of neurons relays those pain signals to a higher brain area called the amygdala, where they trigger your emotional fear response and help you remember to avoid hot skillets in the future.","og_url":"https:\/\/www.salk.edu\/es\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/","og_site_name":"Salk Institute for Biological Studies","article_modified_time":"2024-07-25T18:01:46+00:00","og_image":[{"width":767,"height":767,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/07\/image-sq.png","type":"image\/png"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"6 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/","url":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/","name":"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/#primaryimage"},"thumbnailUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/07\/image-sq.png","datePublished":"2024-07-22T15:40:44+00:00","dateModified":"2024-07-25T18:01:46+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/#breadcrumb"},"inLanguage":"es-MX","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/"]}]},{"@type":"ImageObject","inLanguage":"es-MX","@id":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/#primaryimage","url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/07\/image-sq.png","contentUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/07\/image-sq.png","width":767,"height":767},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/new-tools-reveal-neuropeptides-not-neurotransmitters-encode-danger-in-the-brain\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"Instituto Salk de Estudios Biol\u00f3gicos","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"es-MX"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"Instituto Salk de Estudios Biol\u00f3gicos","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"es-MX","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"hero":"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/07\/han2.png","line_1":"New tools reveal neuropeptides, not fast neurotransmitters, encode danger in the brain","line_2":"Salk scientists create methods to study messenger proteins in the brain called neuropeptides, finding they control the brain\u2019s fear response in mice\u2014a finding that may help develop more effective painkillers and treatments for fear-related conditions like PTSD and anxiety","poster_quote":"","gallery":false,"paper_url":"https:\/\/www.cell.com\/cell\/abstract\/S0092-8674(24)00709-8","journal_title":"Cell","paper_author_list":"Dong-Il Kim, Sekun Park, Seahyung Park, Mao Ye, Jane Y. Chen, Sukjae J. Kang, Jinho Jhang, Avery C. Hunker, Larry S. Zweifel, Kathleen M. Caron, Joan M. Vaughan, Alan Saghatelian, Richard D. Palmiter, Sung Han","doi":"10.1016\/j.cell.2024.06.035","paper_title":"Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit","subhead":"Salk scientists create methods to study messenger proteins in the brain called neuropeptides, finding they control the brain\u2019s fear response in mice\u2014a finding that may help develop more effective painkillers and treatments for fear-related conditions like PTSD and anxiety","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"","descriptive_blurb":"","has_journal_cover":false,"og_image_override":false},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/50243","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":11,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/50243\/revisions"}],"predecessor-version":[{"id":50325,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/50243\/revisions\/50325"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/media\/50252"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/media?parent=50243"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/faculty?post=50243"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disease-research?post=50243"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}