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</style><div class="row feature-box m-0 mb-3"><div class="col-xl-12"><h5 class="mt-2 mb-0"><i class="fa-regular fa-box-archive"></i> Archived Content</h5><p><small>The National Institute of Mental Health archives materials that are over 4 years old and no longer being updated. The content on this page is provided for historical reference purposes only and may not reflect current knowledge or information.</small></p></div></div></div>
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<div class="titleblock">
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<h1 class="titleblock__title" id="title">Brain Circuitry for Positive vs Negative Memories Discovered in Mice</h1>
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<p id="subtitle">Push-pull Control Cinches Causal Connection – NIH Funded Study</p>
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<p class="pagestamp_news_wrap">
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<time class="pagestamp_news_time" datetime="2015-04-29">April 29, 2015</time>
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• <span class="pagestamp_news_type">Press Release</span></p>
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<html><body><p>Neuroscientists have discovered brain circuitry for encoding positive and negative learned associations in mice. After finding that two circuits showed opposite activity following fear and reward learning, the researchers proved that this divergent activity causes either avoidance or reward-driven behaviors. Funded by the National Institutes of Health, they used cutting-edge optical-genetic tools to pinpoint these mechanisms critical to survival, which are also implicated in mental illness.</p>
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<p>“This study exemplifies the power of new molecular tools that can push and pull on the same circuit to see what drives behavior,” explained Thomas R. Insel, M.D., director of NIH’s National Institute of Mental Health (NIMH). “Improved understanding of how such emotional memory works holds promise for solving mysteries of brain circuit disorders in which these mechanisms are disrupted.”</p>
|
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<p>NIMH grantee <a href="http://tyelab.mit.edu/kay-m-tye/" rel="external noreferrer">Kay Tye, Ph.D. <i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>, Praneeth Namburi and Anna Beyeler, Ph.D., of the Massachusetts Institute of Technology (MIT), Cambridge MA, and colleagues, report their findings April 29, 2015 in the journal <em>Nature</em>. </p>
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<p>Prior to the new study, scientists suspected involvement of the circuits ultimately implicated, but were stumped by a seeming paradox. A crossroads of convergent circuits in an emotion hub deep in the brain, the <em>basolateral amygdala</em>, seem to be involved in both fear and reward learning, but how one brain region could orchestrate such opposing behaviors – approach and avoidance – remained an enigma. How might signals find the appropriate path to follow at this fork in the road?</p>
|
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|
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<p>To find out, Tye and colleagues explored whether two suspect circuit projections from the crossroads might hold clues. One projects to a reward center, the <em>nucleus accumbens</em>, and the other to a nearby fear center, the <em>centromedial amygdala</em>, the output station of the emotion hub.</p>
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<p>Each circuit projection is composed of separate populations of intertwined neurons. The researchers first used telltale fluorescent bead tracers to sort out which neurons belonged to each circuit. They then measured an indicator of connectivity – the strength of neural connections – in the projections, after mice underwent fear or reward learning. Animals were trained to either fear a tone paired with a shock or to associate the tone with a sugar reward.</p>
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<p>Strikingly, crossroads connectivity to reward center projections decreased after fear learning and increased with reward learning. By contrast, connectivity to fear center projections increased with fear learning and decreased after reward learning.</p>
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<p>These converging mechanisms in anatomically intertwined circuits could hold clues to teasing apart how positive and negative emotional associations may influence each other, Tye suggested.</p>
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<p>To prove a causal link between the projection-identified circuits and behavior, Tye’s team turned to <a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="be86b68a-acb3-496e-a177-f2434acb7a42" href="/news/science-updates/2014/channel-makeover-bioengineered-to-switch-off-neurons">optogenetics</a>, which enables light pulses to control brain circuitry in animals genetically engineered to be light-responsive. Optically stimulating the reward center projection enhanced positive reinforcement, while stimulating the fear center projection promoted negative reinforcement. Similarly, blocking the fear center projection impaired fear learning and enhanced reward learning.</p>
|
||
|
||
<p>Finally, the researchers pinpointed defining electrophysiological, anatomic and genetic features of the two circuits that help to explain the opposite connectivity responses.</p>
|
||
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<p>“Given that many mental health problems, including anxiety, addiction, and depression, may arise from perturbations in emotional processing, these findings could help to pave the way to a circuit-based approach to treating mental illness,” said Tye.</p>
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<span class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/sites/default/files/images/news-items/tyeinjectretrogradebeads.jpg" width="354" height="217" alt="The researchers pinpointed separate brain circuits for positive and negative associations in mouse brain by injecting retrograde fluorescent bead tracers (green, red) that migrated upstream through neuronal projections linking a reward center (NAc, nucleus accumbens) and a fear center (CeM, centromedial amygdala) to an emotional memory crossroads (BLA, basolateral amygdala).">
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<span class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <img loading="lazy" src="/sites/default/files/images/news-items/tyevideocastposterframe5.jpg" width="550" height="353" alt="MIT neuroscientist Kay Tye, Ph.D., explains the line of research into the brain circuitry of pleasure seeking and pain avoidance that led to the new findings.">
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<p><em>MIT neuroscientist Kay Tye, Ph.D., <a href="http://videocast.nih.gov/launch.asp?18109" rel="external">explains <i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a> the line of research into the brain circuitry of pleasure seeking and pain avoidance that led to the new findings.</em></p>
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<p>See MIT press release:<br>
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<a href="http://newsoffice.mit.edu/2015/neurons-assign-good-bad-emotions-0429" rel="external noreferrer">How the brain tells good from bad <i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a></p>
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