{"id":24439,"date":"2025-05-13T09:15:57","date_gmt":"2025-05-13T16:15:57","guid":{"rendered":"https:\/\/dornsife.usc.edu\/news\/?p=24439"},"modified":"2025-05-13T09:15:59","modified_gmt":"2025-05-13T16:15:59","slug":"molecular-tool-targets-synapses-and-breaks-brain-circuits","status":"publish","type":"post","link":"https:\/\/dornsife.usc.edu\/news\/stories\/molecular-tool-targets-synapses-and-breaks-brain-circuits\/","title":{"rendered":"USC Dornsife researchers develop tool to break brain circuits with molecular precision"},"content":{"rendered":"\n\n\n    \n                                \n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-hero \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-hero\"\n    \n      >\n\n    \n<div class=\"inner-wrapper\">\n          \n<div class=\"f--field f--image\">\n\n    \n    \n    \n    \n    \n    \n              \n      <img\n                            data-src=\"https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/05\/arnold_elife_top-768x432.jpg\"\n          data-srcset=\"https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/05\/arnold_elife_top-1920x1080.jpg 1920w,https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/05\/arnold_elife_top-1280x720.jpg 1280w,https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/05\/arnold_elife_top-768x432.jpg 768w\"          data-sizes=\"(min-width:1200px) 75vw, (min-width:768px) 83vw, 100vw\"          class=\"lazyload\"\n        \n                  alt=\"A neuron with branches speckled with glowing green and purple and a bright green center against a black background\"\n        \n        \n                                      \/>\n\n    \n    \n  \n  \n\n<\/div>\n  \n      <div class=\"image-caption\">\n          \n<div class=\"f--field f--description\">\n\n    \n  Genetically engineered proteins glow within a neuron. (Photo: Courtesy of Don Arnold.)\n\n\n<\/div>\n    <\/div>\n  \n  <div class=\"text-wrapper\">\n          <nav aria-label=\"Breadcrumb\" class=\"breadcrumbs\">\n        <ul>\n                      <li><a href=\"\/news\/stories\/\">News<\/a><\/li>\n                      <li><a href=\"\/news\/stories\/\/?category=science-and-technology\">Science and Technology<\/a><\/li>\n                  <\/ul>\n      <\/nav>\n    \n              \n<div class=\"f--field f--page-title\">\n\n    \n  <h1>USC Dornsife researchers develop tool to break brain circuits with molecular precision<\/h1>\n\n\n<\/div>\n    \n          <div class=\"subtitle\">\n            \n<div class=\"f--field f--description\">\n\n    \n  The reversible method targets specific synapses without harming neurons, offering a powerful tool for studying \u2014 and potentially treating \u2014 conditions such as addiction, epilepsy and PTSD.\n\n\n<\/div>\n      <\/div>\n    \n           <strong class=\"author-field\"><span >By<\/span><a href=\"mailto:communication@dornsife.usc.edu\">Darrin S. Joy<\/a><\/strong>\n    \n          <span class=\"post-date-field\">May 13, 2025<\/span>\n      <\/div>\n<\/div>\n\n\n  <\/div><\/div>\n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--social-share \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--social-share\"\n    \n      >\n\n    \n  <div class=\"content-wrapper\">\n    <span class=\"a2a_kit a2a_kit_size_32 addtoany_list\" style=\"line-height: 32px;\">\n      <span class=\"title\">\n        Share\n      <\/span>\n                        <a class=\"a2a_button_copy_link\" target=\"_blank\" href=\"\/#copy_link\" rel=\"nofollow noopener\" title=\"Link\">\n            <span class=\"a2a_svg a2a_s__default a2a_s_copy_link\">\n              <svg height=\"19\" viewBox=\"0 0 19 19\" width=\"19\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"m7.43475275 9.52380952-2.17490843 2.26076008c-1.08745421 1.058837-1.68841575 2.518315-1.68841575 4.0350275 0 1.5167124.60096154 2.9475732 1.68841575 4.0350274 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xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"m8.14285714 9.42857143c-.17142857 0-.34285714 0-.51428571.08571428l7.28571427 6.34285719c.3428572.2571428.6857143.2571428.9428572 0l7.2857142-6.34285719c-.0857142-.08571428-.2571428-.08571428-.4285714-.08571428zm-1.28571428 1.11428567v.1714286 8.5714286c0 .6857143.6 1.2857143 1.28571428 1.2857143h14.57142856c.6857143 0 1.2857143-.6 1.2857143-1.2857143v-8.5714286c0-.0857143 0-.0857143 0-.1714286l-7.2 6.3428572c-.7714286.6857143-1.8857143.6857143-2.6571429 0z\" fill-rule=\"evenodd\" transform=\"translate(-6 -9)\"\/><\/svg>\n            <\/span>\n            <span class=\"a2a_label visually-hidden\">Email<\/span>\n          <\/a>\n                  <\/span>\n  <\/div>\n\n  <\/div><\/div>\n \n\n\n        \n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-highlights \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-highlights\"\n    \n      >\n\n    \n<div class=\"inner-wrapper\">\n          \n<div class=\"f--field f--section-title\">\n\n    \n  <h2>\n          Key takeways:\n      <\/h2>\n\n\n<\/div>\n    \n      <ul>\n              <li><p>USC Dornsife scientists have developed tools that can now interrupt specific links between neurons, called synapses, enabling targeted study of brain circuits.<\/p>\n<\/li>\n              <li><p>The method targets either excitatory or inhibitory synapses with molecular precision, leaving the rest of the neuron unharmed.<\/p>\n<\/li>\n              <li><p>The process is reversible, allowing researchers to study how specific circuits influence behavior, perception and neurological disorders.<\/p>\n<\/li>\n              <li><p>The technology could one day help guide therapies for conditions such as epilepsy, PTSD and addiction.<\/p>\n<\/li>\n          <\/ul>\n  <\/div>\n  \n\n  <\/div><\/div>\n\n\n\n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--rich-text \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--rich-text\"\n    \n      >\n\n    \n      \n<div class=\"f--field f--wysiwyg\">\n\n    \n  <p>Scientists have developed a powerful new method for selectively and reversibly breaking connections between brain cells <em>\u2014<\/em> a leap forward that could transform how we study the brain processes and, one day, how we treat neurological disorders such as epilepsy, addiction and post-traumatic stress disorder.<\/p>\n<p>The <a href=\"https:\/\/elifesciences.org\/articles\/103757\" target=\"_blank\" rel=\"noopener\">study<\/a>, led by USC Dornsife College of Letters, Arts and Sciences neurobiologist <a href=\"https:\/\/dornsife.usc.edu\/profile\/donald-arnold\/\">Don Arnold <\/a>and published in <em>eLife<\/em>, introduces a suite of genetically engineered tools that allow researchers to eliminate either excitatory or inhibitory synapses <em>\u2014<\/em> the specialized junctions where neurons communicate <em>\u2014<\/em> with molecular precision. Crucially, the technique affects only the targeted synapses, leaving the rest of the neuron intact.<\/p>\n<p>This level of specificity, Arnold says, marks a first in neuroscience. \u201cAs far as I know, no one else has ever been able to ablate [knock out] specific synapses without affecting the whole neuron,\u201d he said.<\/p>\n<p>The ability to selectively dismantle parts of a neural network \u2014 and then allow them to regrow \u2014 opens new paths to understanding how microcircuits in the brain govern perception, behavior and memory.<\/p>\n<p>Arnold, professor of <a href=\"https:\/\/dornsife.usc.edu\/bisc\/\">biological sciences<\/a> and biomedical engineering, and <a href=\"https:\/\/dornsife.usc.edu\/arnold\/\">his team<\/a> created two molecular tools \u2014 one that targets excitatory synapses and another that targets inhibitory ones \u2014 using an approach inspired by the brain\u2019s own system for recycling proteins. The technique involves E3 ligases, enzymes that normally help dispose of damaged proteins by tagging them with a molecule called ubiquitin. Once tagged, the proteins are sent to the proteasome \u2014 a cellular structure Arnold likens to a \u201cminiature wood-chipper\u201d \u2014 to be broken down and repurposed.<\/p>\n<p>In this study, the researchers paired the E3 ligases with <a href=\"https:\/\/www.nature.com\/articles\/s41592-025-02670-x\" target=\"_blank\" rel=\"noopener\">antibody-like proteins<\/a> that bind to specific synaptic scaffolding proteins. The result: a custom-built tool that directs the brain\u2019s trash-disposal system to eliminate key components of either excitatory or inhibitory synapses \u2014 even though they\u2019re healthy. Without their molecular scaffolding, the synapses fall apart and the neuron cannot transmit the signal to the next neuron, disrupting the circuit.<\/p>\n<p>Arnold named the tools PFE3 and GFE3, which target excitatory and inhibitory synapses respectively. He also developed two versions of GFE3 that can be activated on demand: one by light (paGFE3) and one by a chemical signal (chGFE3).<\/p>\n<p>Significantly, the effects are reversible. When expression of the tools is turned off, neurons regrow their lost synapses within days. That feature gives researchers the power not just to remove a connection and observe the result \u2014 but to restore it and observe the recovery.<\/p>\n<p>\u201cThis reversibility and the ability to target synapses so specifically make this method uniquely powerful for studying brain circuits,\u201d Arnold said.<\/p>\n<p>While potential therapeutic use is still far off, the technology could eventually guide the development of treatments that target malfunctioning brain circuits with unprecedented precision, leaving healthy ones untouched.<\/p>\n\n\n\n<\/div>\n\n\n  <\/div><\/div>\n\n\n\n  \n        \n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-related-stories \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-related-stories\"\n    \n      >\n\n    \n  <div class=\"inner-wrapper\">\n              \n<div class=\"f--field f--section-title\">\n\n    \n  <h2>\n          Related Articles\n      <\/h2>\n\n\n<\/div>\n    \n                  <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/mu-opioid-receptor-structural-change-revealed-by-cryo-em\/\" \n                        class=\"\" \n      >A path to safer painkillers \u2013 revealed by freezing opioids and their protein receptors in motion<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n              <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/teen-anxiety-prediction-improves-with-combined-fmri-and-eeg-brain-scans\/\" \n                        class=\"\" \n      >For predicting teen anxiety, 2 brains scans are better than 1<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n              <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/alzheimers-and-financial-scam-vulnerability-may-be-linked\/\" \n                        class=\"\" \n      >Falling for financial scams? It may signal early Alzheimer\u2019s disease<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n            <\/div>\n\n\n  <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"<p>The reversible method targets specific synapses without harming neurons, offering a powerful tool for studying \u2014 and potentially treating \u2014 conditions like addiction, epilepsy and PTSD.<\/p>\n","protected":false},"author":13,"featured_media":24440,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[16],"tags":[113,745,60],"class_list":["post-24439","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-and-technology","tag-brain","tag-neurobiology","tag-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.1.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>USC Dornsife researchers 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