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<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="yJ05TQAh4MG5986DQj5f4PGHP1YmYs8JPwKawG3DEntz3zcttCIhyXcln5GyR3G3">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="yJ05TQAh4MG5986DQj5f4PGHP1YmYs8JPwKawG3DEntz3zcttCIhyXcln5GyR3G3">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="yJ05TQAh4MG5986DQj5f4PGHP1YmYs8JPwKawG3DEntz3zcttCIhyXcln5GyR3G3">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="yJ05TQAh4MG5986DQj5f4PGHP1YmYs8JPwKawG3DEntz3zcttCIhyXcln5GyR3G3">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="yJ05TQAh4MG5986DQj5f4PGHP1YmYs8JPwKawG3DEntz3zcttCIhyXcln5GyR3G3">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="21521618">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://linkinghub.elsevier.com/retrieve/pii/S0896-6273(11)00201-7"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21521618&amp;db=pubmed&amp;nlmid=8809320"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="21521618"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21521618/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21521618&amp;db=pubmed&amp;nlmid=8809320"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21521618"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/21521618/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21521618/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="21521618" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F21521618%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="yJ05TQAh4MG5986DQj5f4PGHP1YmYs8JPwKawG3DEntz3zcttCIhyXcln5GyR3G3"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
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In cerebral cortex there is a developmental switch from NR2B- to NR2A-containing NMDA receptors (NMDARs) driven by activity and sensory experience. This subunit switch alters NMDAR function, influences synaptic plasticity, and its dysregulation is associated with neurological disorders. However, the mechanisms driving the subunit switch are not known. Here, we show in hippocampal CA1 pyramidal neurons that the NR2B to NR2A switch driven acutely by activity requires activation of NMDARs and mGluR5, involves PLC, Ca(2+) release from IP(3)R-dependent stores, and PKC activity. In mGluR5 knockout mice the developmental NR2B-NR2A switch in CA1 is deficient. Moreover, in visual cortex of mGluR5 knockout mice, the NR2B-NR2A switch evoked in vivo by visual experience is absent. Thus, we establish that mGluR5 and NMDARs are required for the activity-dependent NR2B-NR2A switch and play a critical role in experience-dependent regulation of NMDAR subunit composition in vivo.
</p>
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<p class="copyright" id="copyright">
Copyright © 2011 Elsevier Inc. All rights reserved.
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<div class="figures" id="figures">
<h2 class="title">
Figures
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<div class="figures-list" id="slides-container"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/e623a681453e/nihms-283259-f0001.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-0"
role="button"
data-image-width="715"
data-image-height="565"
data-image-alt="Figure 1"
data-pmc-id="PMC3087383"
data-figure-id="F1">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/38638e9cecc0/nihms-283259-f0001.gif"
alt="Figure 1" />
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<strong class="figure-label">
<p> Figure 1. Activity-dependent switch from NR2B- to… </p>
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<p> Figure 1. Activity-dependent switch from NR2B- to NR2A-containing NMDARs at hippocampal CA1 pyramidal cell synapses </p>
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<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1. Activity-dependent switch from NR2B- to NR2A-containing NMDARs at hippocampal CA1 pyramidal cell synapses
</strong>
<div class="figure-caption-contents">(A) Summary data of NMDA EPSC peak amplitude vs. time plot for two independent pathways onto the same cell. In one pathway (test; red) the induction protocol was applied, ifenprodil (5 μM) was bath-applied at the time indicated. (B) NMDA EPSCs from example experiments for the test and control pathways taken at the times indicated in A. For this and the other figures, NMDA EPSCs typically didnt exhibit any change in peak amplitude after the induction protocol and so are shown superimposed with no amplitude rescaling. (C) NMDA EPSCs from an example experiment showing changes in the ifenprodil sensitivity in the control and test paths after application of the induction protocol. (D) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in the control and test paths, before and after the induction protocol (control path: pre-induction = 282 ± 23 ms, post-induction = 277 ± 22 ms; test path: pre-induction = 285 ± 22 ms, post-induction = 218 ± 16 ms). (E) Summary graph for EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude (control path = 41 ± 4.1 %; test path = 76 ± 6.2 %). n = 15 cells throughout; slices prepared from P5-7 rat; * indicates P &lt; 0.05.</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="452"
data-image-height="747"
data-image-alt="Figure 2"
data-pmc-id="PMC3087383"
data-figure-id="F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/f4f085fa75b2/nihms-283259-f0002.gif"
alt="Figure 2" />
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<strong class="figure-label">
<p> Figure 2. mGluR5 and NMDAR activation are… </p>
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<strong class="figure-label">
<p> Figure 2. mGluR5 and NMDAR activation are required for the activity-dependent switch in NR2 subunit… </p>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2. mGluR5 and NMDAR activation are required for the activity-dependent switch in NR2 subunit composition
</strong>
<div class="figure-caption-contents">(A) Summary data of NMDA EPSC peak amplitude vs. time plot for two independent pathways onto the same cell performed in the presence of bath-applied MTEP (10 μM). In one pathway (test; red) the induction protocol was applied, ifenprodil (5 μM) was bath-applied at the time indicated (n = 10). (B) NMDA EPSCs from example experiments for the test and control pathways taken from the experiments in A. (C) NMDA EPSCs from an example experiment showing changes in the ifenprodil sensitivity in the control and test paths after application of the induction protocol. (D-F) As for A-C, but in the presence of LY367385 (100 μM; n = 7). (G-I) As for A-C, but in the presence of D-AP5 (50 μM; n = 8). (J) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in the control and test paths, before and after the induction protocol in the presence of the different antagonists (control path: MTEP = 289 ± 8.2 ms, LY367385 = 298 ± 10.5 ms, not paired = 293 ± 14.3 ms, AP5 = 299 ± 11.2 ms, cycloheximide = 302 ± 13.5 ms; test path: MTEP = 282 ± 9.1 ms, LY367385 = 225 ± 11.8 ms, not paired = 276 ± 16.5 ms, AP5 = 302 ± 13.1 ms, cycloheximide = 228 ± 11.5 ms). (K) Summary graph for EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude in the presence of the different antagonists (control path: MTEP = 45.2 ± 5.1 %, LY367385 = 42.1 ± 4.9 %, not paired = 41.1 ± 4.8 %, AP5 = 44.4 ± 5.2 %, cycloheximide = 39.5 ± 4.8 %; test path: MTEP = 52.3 ± 6.0 %, LY367385 = 72.1 ± 7.5 %, not paired = 51.5 ± 5.3 %, AP5 = 45.6 ± 4.5 %, cycloheximide = 64.5 ± 6.1 %).</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="452"
data-image-height="746"
data-image-alt="Figure 3"
data-pmc-id="PMC3087383"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/e3868a60e729/nihms-283259-f0003.gif"
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<strong class="figure-label">
<p> Figure 3. Signaling requirements for the activity-dependent… </p>
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<strong class="figure-label">
<p> Figure 3. Signaling requirements for the activity-dependent switch in NR2 subunit composition </p>
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<div class="figure-caption-contents"><p> (A) Summary data… </p></div>
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<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3. Signaling requirements for the activity-dependent switch in NR2 subunit composition
</strong>
<div class="figure-caption-contents">(A) Summary data of NMDA EPSC peak amplitude vs. time plot for two independent pathways onto the same cell performed in the presence of bath-applied U73122 (5 μM). In one pathway (test; red) the induction protocol was applied, ifenprodil (5 μM) was bath-applied at the time indicated (n = 6). (B) NMDA EPSCs from example experiments for the test and control pathways taken from the experiments in A. (C) NMDA EPSCs from an example experiment showing changes in the ifenprodil sensitivity in the control and test paths after application of the induction protocol. (D-F) As for A-C, but in the presence of GFX109203 (1 μM; n = 8). (G-I) As for A-C, but in the presence of H89 (10 μM; n = 6) (J) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in the control and test paths, before and after the induction protocol in the presence of a number of different antagonists (control path: BAPTA = 280 ± 12 ms, thapsigargin = 298 ± 14 ms, heparin = 278 ± 13 ms, 2APB = 302 ± 11 ms, U73122 = 293 ± 14 ms, GF109203X = 305 ± 10 ms, KN93 = 298 ± 11 ms, H89 = 311 ± 14 ms; test path: BAPTA = 271 ± 9 ms, thapsigargin = 276 ± 16 ms, heparin = 265 ± 14 ms, 2APB = 289 ± 13 ms, U73122 = 286 ± 14 ms, GF109203X = 296 ± 13 ms, KN93 = 228 ± 14 ms, H89 = 241 ± 12 ms). (K) Summary graph for EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude in the presence of the different antagonists (control path: BAPTA = 39.8 ± 6.2 %, thapsigargin = 42.1 ± 7.9 %, heparin = 38.6 ± 4.3 %, 2APB = 44.9 ± 6.7%, U73122 = 43.9 ± 4.9 %, GF109203X = 43.2 ± 6.9 %, KN93 = 39.6 ± 6.4 %, H89 = 40.3 ± 5.5 %; test path: BAPTA = 40.1 ± 5.0 %, thapsigargin = 49.1 ± 5.7 %, heparin = 40.6 ± 5.6 %, 2APB = 41.6 ± 5.2 %, U73122 = 42.6 ± 3.8 %, GF109203X = 39.5 ± 8.0 %, KN93 = 68.0 ± 7.2 %, H89 = 71.1 ± 6.5 %). Horizontal lines indicate the average value in the control path in absence of pharmacological agents; * indicates P &lt; 0.05. Summary data expressed as average ± sem. BAPTA, 10 mM, n = 6; thapsigargin, 5 μM, n = 7; heparin, 10 mg/mL, n = 6; 2APB, 100 μM, n = 7; GF109203X, 1 μM, n = 8; KN93, 10 μM, n = 7</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="488"
data-image-height="755"
data-image-alt="Figure 4"
data-pmc-id="PMC3087383"
data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/2e33fcfc07c4/nihms-283259-f0004.gif"
alt="Figure 4" />
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<strong class="figure-label">
<p> Figure 4. The activity-dependent switch in NR2… </p>
</strong>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4. The activity-dependent switch in NR2 subunit composition induced in mouse hippocampal slices </p>
</strong>
<div class="figure-caption-contents"><p> (A)… </p></div>
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<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4. The activity-dependent switch in NR2 subunit composition induced in mouse hippocampal slices
</strong>
<div class="figure-caption-contents">(A) Summary data of NMDA EPSC peak amplitude vs. time plot for two independent pathways onto the same cell performed in mouse hippocampal slice (prepared from P5-7 mouse). In one pathway (test; red) the induction protocol (100 Hz tetanus for 6 s) was applied prior to the start of whole-cell recording, ifenprodil (5 μM) was bath-applied at the time indicated (n = 9). (B) NMDA EPSCs from example experiments for the test and control pathways taken from the experiments in A. (C) NMDA EPSCs from an example experiment showing changes in the ifenprodil sensitivity in the control and test paths after application of the induction protocol. (D-F) As for A-C, but in the presence of MTEP (10 μM; n = 8). (G-I) As for A-C, but in the presence of U73122 (5 μM; n = 7). (J) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in the control and test paths, before and after the induction protocol in control (CT) and in the presence of the different antagonists (control path: CT = 330 ± 20 ms, MTEP = 323 ± 17 ms, U73122 = 318 ± 23 ms, APV = 305 ± 12 ms; test path: CT = 229 ± 14 ms, MTEP = 312 ± 15 ms, U73122 = 307 ± 18 ms, APV = 300 ± 15 ms). (K) Summary graph for EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude (control path: CT = 41.7 ± 4.1 %, MTEP = 44.9 ± 5.8 %, U73122 = 41.0 ± 3.5 %, APV = 39.5 ± 6.9 %; test path: CT = 66.4 ± 3.3 %, MTEP = 47.4 ± 4.6 %, U73122 = 43.4 ± 6.2 %, APV = 44.6 ± 5.8 %).</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
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data-image-alt="Figure 5"
data-pmc-id="PMC3087383"
data-figure-id="F5">
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id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/3e181a257029/nihms-283259-f0005.gif"
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<strong class="figure-label">
<p> Figure 5. Impaired activity-dependent NR2 subunit switch… </p>
</strong>
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<strong class="figure-label">
<p> Figure 5. Impaired activity-dependent NR2 subunit switch in the mGluR5 knock-out mice </p>
</strong>
<div class="figure-caption-contents"><p> (A) Summary data… </p></div>
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<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5. Impaired activity-dependent NR2 subunit switch in the mGluR5 knock-out mice
</strong>
<div class="figure-caption-contents">(A) Summary data of NMDA EPSC peak amplitude vs. time plot for two independent pathways onto the same cell performed in hippocampal slice from mGluR5 heterozygous (het) mouse (P5-7). In one pathway (test; red) the induction protocol (100 Hz tetanus for 6 s) was applied prior to the start of whole-cell recording, ifenprodil (5 μM) was bath-applied at the time indicated (n = 16 mice). (B) NMDA EPSCs from example experiments for the test and control pathways taken from the experiments in A. (C) NMDA EPSCs from an example experiment showing changes in the ifenprodil sensitivity in the control and test paths after application of the induction protocol. (D-F) As for A-C, but for mGluR5 knock-out (KO) (n = 9 mice). (G) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in the control and test paths, before and after the induction protocol in mGluR5 heterozygous mice (het) and mGluR5 knock-out (KO) (control path: het = 358 ± 8 ms, KO = 361 ± 14 ms; test path: het = 284 ± 10 ms, KO = 338 ± 29 ms). (H) Summary graph for EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude (control path: het = 41.0 ± 6.9 %, KO = 37.9 ± 2.6 %; test path: het = 68.2 ± 3.7 %, KO = 52.8 ± 6.5 %).</div>
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data-image-height="756"
data-image-alt="Figure 6"
data-pmc-id="PMC3087383"
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<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745a/3087383/8601a62fa949/nihms-283259-f0006.gif"
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<p> Figure 6. Impaired developmental switch in NR2… </p>
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<strong class="figure-label">
<p> Figure 6. Impaired developmental switch in NR2 subunit composition in hippocampus and primary visual cortex… </p>
</strong>
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Figure 6. Impaired developmental switch in NR2 subunit composition in hippocampus and primary visual cortex ofmGluR5 knock-out mice
</strong>
<div class="figure-caption-contents">(A) Scaled NMDA EPSCs from hippocampal example experiments taken from wild type (WT, black) and mGluR5 knock-out (KO, red). (B) NMDA EPSCs from hippocampal example experiments taken showing ifenprodil sensitivity. (C) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in wild type (WT) and mGluR5 knock-out (KO) at P15-18 (WT = 195 ± 8 ms, KO = 238 ± 10 ms). (D) Summary graph for EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude for wild type (WT) and mGluR5 knock-out (KO) at P15-18 (WT = 75.4 ± 4.0 %, KO = 53.0 ± 3.6 %). n = 8 mice (E-H) As for A-D, but for layer 4 inputs onto layer 2/3 pyramidal neurons in primary visual cortex from P15-19 mice (decay kinetics: WT = 209 ± 9 ms, KO = 249 ± 13 ms; ifenprodil sensitivity: WT = 67.4 ± 5.3 %, KO = 48.7 ± 3.4 %). n = 8 mice. *p &lt; 0.05</div>
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data-figure-id="F7">
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<p> Figure 7. Impaired sensory-experience switch in the… </p>
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<strong class="figure-label">
<p> Figure 7. Impaired sensory-experience switch in the NR2 subunit composition in mGluR5 knock-out mice </p>
</strong>
<div class="figure-caption-contents"><p> (A)… </p></div>
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<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 7. Impaired sensory-experience switch in the NR2 subunit composition in mGluR5 knock-out mice
</strong>
<div class="figure-caption-contents">(A) Scaled NMDA EPSCs from dark-reared wild type (WT, top) or mGluR5 knock out mice (KO, bottom) without (black trace for WT and green trace for KO) or with (red traces) 2.5 hours light experience (LE). (B) Example traces for ifenprodil sensitivity in dark-reared wild type mice (WT) without light experience (LE, top) or with light experience (+LE, bottom). (C) Example traces for ifenprodil sensitivity in dark-reared mGluR5 knock-out mice (KO) without light experience (LE, top) or with light experience (+LE, bottom). (D) Summary graph showing the average values for the weighted time constant (τ<sub>w</sub>) in wild type (WT) and mGluR5 knock-out (KO) with or without LE (WT = 267 ± 18 ms, WT LE = 210 ± 9ms, KO = 271 ± 10 ms, KO LE = 250 ± 8 ms). (E) Summary graph for NMDAR EPSC amplitude in the presence of ifenprodil expressed as percentage of pre-ifenprodil amplitude for wild type (WT) and mGluR5 knock-out (KO) with or without LE (WT = 49.4 ± 3.8 %, WT LE = 61.5 ± 3.7 %, KO = 47.6 ± 3.9 %, KO LE = 53.5 ± 3.6 %). n = 10 animals, *p &lt; 0.05</div>
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<p> Figure 8. Mechanism for the activity-dependent switch… </p>
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<p> Figure 8. Mechanism for the activity-dependent switch in NR2 subunit composition </p>
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Figure 8. Mechanism for the activity-dependent switch in NR2 subunit composition
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<div class="figure-caption-contents">Schematic of a dendritic spine showing the receptors and signaling pathways involved in the activity-dependent NR2 subunit switch. The pharmacological agents used to block the activity-dependent switch are also shown.</div>
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