{"id":13823,"date":"2020-01-16T09:30:32","date_gmt":"2020-01-16T14:30:32","guid":{"rendered":"https:\/\/biology.mit.edu\/?p=13823"},"modified":"2020-10-28T20:40:47","modified_gmt":"2020-10-29T00:40:47","slug":"with-these-neurons-extinguishing-fear-is-its-own-reward","status":"publish","type":"post","link":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/","title":{"rendered":"With these neurons, extinguishing fear is its own reward"},"content":{"rendered":"
\n
\n
\n
\n

When you expect a really bad experience to happen and then it doesn\u2019t, it\u2019s a distinctly positive feeling. A new study of fear extinction training in mice may suggest why: The findings not only identify the exact population of brain cells that are key for learning not to feel afraid anymore, but also show these neurons are the same ones that help encode feelings of reward.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n

The study, published Jan. 14 in\u00a0Neuron<\/em>\u00a0by scientists at MIT\u2019s Picower Institute for Learning and Memory, specifically shows that fear extinction memories and feelings of reward alike are stored by neurons that express the gene Ppp1r1b in the posterior of the basolateral amygdala (pBLA), a region known to assign\u00a0associations of\u00a0aversive or rewarding\u00a0feelings, or \u201cvalence,\u201d with memories.\u00a0The study was conducted by Xiangyu Zhang, a graduate student, Joshua Kim, a former graduate student, and\u00a0Susumu Tonegawa<\/a>, Professor of Biology and Neuroscience at RIKEN-MIT Laboratory of Neural Circuit Genetics at the Picower Institute for Learning and Memory at MIT and Howard Hughes Medical Institute.<\/p>\n

\u201cWe constantly live at the balance of positive and negative emotion,\u201d Tonegawa said. \u201cWe need to have very strong memories of dangerous circumstances in order to avoid\u00a0similar circumstances to recur. But if we are constantly feeling threatened we can become depressed. You need a way to bring your emotional state back to something more positive.\u201d<\/p>\n

Overriding fear with reward<\/strong><\/p>\n

In a prior study, Kim showed that Ppp1r1b-expressing neurons encode rewarding valence and compete with distinct Rspo2-expressing neurons in the BLA that encode negative valence. In the new study, Zhang, Kim and Tonegawa set out to determine whether this competitive balance also underlies fear and its extinction.<\/p>\n

In fear extinction, an original fearful memory is\u00a0thought to be\u00a0essentially overwritten by a new memory that is not fearful. In the study, for instance, mice were exposed to little shocks in\u00a0a\u00a0chamber, making them\u00a0freeze due to the formation of\u00a0fearful\u00a0memory.\u00a0But the next day,\u00a0when the\u00a0mice were returned to the\u00a0same chamber for a longer period of time without\u00a0any\u00a0further little shocks,\u00a0freezing gradually dissipated\u00a0and hence this treatment is called fear extinction training. The fundamental question then is whether the fearful memory is lost or just suppressed by the formation of a new memory during the fear extinction training.<\/p>\n

While the mice underwent fear extinction training the scientists watched the activity of the different neural populations in the BLA. They saw that Ppp1r1b cells were more active and Rspo2 cells were less active in mice that experienced fear extinction. They also saw that while Rspo2 cells were mostly activated by the shocks and were inhibited during fear extinction, Ppp1r1b cells were mostly active during extinction memory training and retrieval, but were inhibited during the shocks.<\/p>\n

These and other experiments suggested\u00a0to the authors\u00a0that\u00a0the hypothetical fear extinction memory may be formed\u00a0in the Ppp1r1b\u00a0neuronal population\u00a0and the team\u00a0went on to\u00a0demonstrate this vigorously. For this, they employed the technique previously pioneered in their lab for the identification and manipulation of the neuronal population that holds specific memory information, memory \u201cengram\u201d cells.\u00a0\u00a0Zhang labeled\u00a0Ppp1r1b neurons that were activated during\u00a0retrieval of\u00a0fear extinction memory\u00a0with the light-sensitive protein channelrhodopsin.\u00a0When\u00a0these neurons were activated by blue laser light during a second round of fear extinction training it enhanced and accelerated the extinction.\u00a0Moreover,\u00a0when\u00a0the engram cells\u00a0were inhibited\u00a0by another optogenetic technique,\u00a0fear extinction\u00a0was impaired\u00a0because the Ppp1r1b engram neurons\u00a0could\u00a0no longer suppress the Rspo2 fear neurons. That allowed the fear memory to regain primacy.<\/p>\n

These data met the fundamental criteria for the existence of engram cells for fear extinction memory within the pBLA Ppp1r1b cell population: activation and reactivation by recall and enduring and off-line maintenance of the acquired extinction memory.<\/p>\n

<\/div>\n

Because Kim had previously shown Ppp1r1b neurons are activated by rewards and drive appetitive behavior and memory, the team sequentially tracked Ppp1r1b cell activity in mice that eagerly received water reward followed by food reward followed by fear extinction training and fear extinction memory retrieval. The overlap of Ppp1r1b neurons activated by fear extinction vs. water reward was as high as the overlap of neurons activated by water vs. food reward. And finally, artificial optogenetic activation of Ppp1r1b extinction memory engram cells was as effective as optogenetic activation of Ppp1r1b water reward-activated neurons in driving appetitive behaviors. Reciprocally, artificial optogenetic activation of water-responding Ppp1r1b neurons enhanced fear extinction training as efficiently as optogenetic activation of fear extinction memory engram cells. These results demonstrate that fear extinction is equivalent to bona fide rewards and therefore provide the neuroscientific basis for the widely held experience in daily life: omission of expected punishment is a reward.<\/p>\n

What next?<\/strong><\/p>\n

By establishing this intimate connection between fear extinction and reward\u00a0and by identifying a genetically defined neuronal population (Ppp1r1b) that plays a crucial role in fear extinction this study provides potential therapeutic targets for treating fear disorders like PTSD and anxiety, Zhang said.<\/p>\n

From the basic scientific point of view, Tonegawa said, how fear extinction training specifically activates Ppp1r1b neurons would be an important question to address. More imaginatively,\u00a0results showing how Ppp1r1b neurons override Rspo2 neurons in fear extinction raises an intriguing question about whether a reciprocal dynamic might also occur in the brain and behavior. Investigating \u201cjoy extinction\u201d via these mechanisms might be\u00a0an\u00a0interesting\u00a0research topic.<\/p>\n

The research was supported by the RIKEN Brain Science Institute, the Howard Hughes Medical Institute and the JPB Foundation funded the research.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

When you expect a really bad experience to happen and then it doesn\u2019t, it\u2019s a distinctly positive feeling. A new study of fear extinction training in mice may suggest why: The findings not only identify the exact population of brain cells that are key for learning not to feel afraid anymore, but also show these […]<\/p>\n","protected":false},"author":16,"featured_media":13824,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-13823","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","placement-placement-homepage","research-area-neurobiology"],"acf":[],"yoast_head":"\nWith these neurons, extinguishing fear is its own reward - MIT Department of Biology<\/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:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"With these neurons, extinguishing fear is its own reward\" \/>\n<meta property=\"og:description\" content=\"When you expect a really bad experience to happen and then it doesn\u2019t, it\u2019s a distinctly positive feeling. A new study of fear extinction training in mice may suggest why: The findings not only identify the exact population of brain cells that are key for learning not to feel afraid anymore, but also show these […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/\" \/>\n<meta property=\"og:site_name\" content=\"MIT Department of Biology\" \/>\n<meta property=\"article:published_time\" content=\"2020-01-16T14:30:32+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-10-29T00:40:47+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"2000\" \/>\n\t<meta property=\"og:image:height\" content=\"1042\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Raleigh McElvery\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Raleigh McElvery\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/\",\"url\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/\",\"name\":\"With these neurons, extinguishing fear is its own reward - MIT Department of Biology\",\"isPartOf\":{\"@id\":\"https:\/\/biology.mit.edu\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg\",\"datePublished\":\"2020-01-16T14:30:32+00:00\",\"dateModified\":\"2020-10-29T00:40:47+00:00\",\"author\":{\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66\"},\"breadcrumb\":{\"@id\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#primaryimage\",\"url\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg\",\"contentUrl\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg\",\"width\":2000,\"height\":1042,\"caption\":\"Brain\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\/\/biology.mit.edu\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"With these neurons, extinguishing fear is its own reward\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/biology.mit.edu\/#website\",\"url\":\"https:\/\/biology.mit.edu\/\",\"name\":\"MIT Department of Biology\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/biology.mit.edu\/?s={search_term_string}\"},\"query-input\":\"required name=search_term_string\"}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66\",\"name\":\"Raleigh McElvery\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/image\/\",\"url\":\"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g\",\"contentUrl\":\"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g\",\"caption\":\"Raleigh McElvery\"},\"url\":\"https:\/\/biology.mit.edu\/author\/rmcelvery\/\"}]}<\/script>\n","yoast_head_json":{"title":"With these neurons, extinguishing fear is its own reward - MIT Department of Biology","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:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/","og_locale":"en_US","og_type":"article","og_title":"With these neurons, extinguishing fear is its own reward","og_description":"When you expect a really bad experience to happen and then it doesn\u2019t, it\u2019s a distinctly positive feeling. A new study of fear extinction training in mice may suggest why: The findings not only identify the exact population of brain cells that are key for learning not to feel afraid anymore, but also show these […]","og_url":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/","og_site_name":"MIT Department of Biology","article_published_time":"2020-01-16T14:30:32+00:00","article_modified_time":"2020-10-29T00:40:47+00:00","og_image":[{"width":2000,"height":1042,"url":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg","type":"image\/jpeg"}],"author":"Raleigh McElvery","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Raleigh McElvery","Est. reading time":"5 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/","url":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/","name":"With these neurons, extinguishing fear is its own reward - MIT Department of Biology","isPartOf":{"@id":"https:\/\/biology.mit.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#primaryimage"},"image":{"@id":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#primaryimage"},"thumbnailUrl":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg","datePublished":"2020-01-16T14:30:32+00:00","dateModified":"2020-10-29T00:40:47+00:00","author":{"@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66"},"breadcrumb":{"@id":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/"]}]},{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#primaryimage","url":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg","contentUrl":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2020\/01\/Brain.jpg","width":2000,"height":1042,"caption":"Brain"},{"@type":"BreadcrumbList","@id":"https:\/\/biology.mit.edu\/with-these-neurons-extinguishing-fear-is-its-own-reward\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/biology.mit.edu\/"},{"@type":"ListItem","position":2,"name":"With these neurons, extinguishing fear is its own reward"}]},{"@type":"WebSite","@id":"https:\/\/biology.mit.edu\/#website","url":"https:\/\/biology.mit.edu\/","name":"MIT Department of Biology","description":"","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/biology.mit.edu\/?s={search_term_string}"},"query-input":"required name=search_term_string"}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66","name":"Raleigh McElvery","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/image\/","url":"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g","caption":"Raleigh McElvery"},"url":"https:\/\/biology.mit.edu\/author\/rmcelvery\/"}]}},"_links":{"self":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/13823"}],"collection":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/comments?post=13823"}],"version-history":[{"count":3,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/13823\/revisions"}],"predecessor-version":[{"id":17574,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/13823\/revisions\/17574"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/media\/13824"}],"wp:attachment":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/media?parent=13823"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/categories?post=13823"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/tags?post=13823"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}