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Neurosci."],"accepted":{"date-parts":[[2024,7,30]]},"published-print":{"date-parts":[[2024,9,11]]},"abstract":"<jats:p>\n                    Neuronal excitatory synapses are primarily located on small dendritic protrusions called spines. During synaptic plasticity underlying learning and memory, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through postsynaptic NMDA-type glutamate receptors (NMDARs) initiates signaling pathways that coordinate changes in dendritic spine structure and synaptic function. During long-term potentiation (LTP), high levels of NMDAR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx promote increases in both synaptic strength and dendritic spine size through activation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent protein kinases. In contrast, during long-term depression (LTD), low levels of NMDAR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx promote decreased synaptic strength and spine shrinkage and elimination through activation of the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent protein phosphatase calcineurin (CaN), which is anchored at synapses via the scaffold protein A-kinase anchoring protein (AKAP)150. In Alzheimer's disease (AD), the pathological agent amyloid-\u03b2 (A\u03b2) may impair learning and memory through biasing NMDAR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling pathways toward LTD and spine elimination. By employing AKAP150 knock-in mice of both sexes with a mutation that disrupts CaN anchoring to AKAP150, we revealed that local, postsynaptic AKAP\u2013CaN\u2013LTD signaling was required for A\u03b2-mediated impairment of NMDAR synaptic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx, inhibition of LTP, and dendritic spine loss. Additionally, we found that A\u03b2 acutely engages AKAP\u2013CaN signaling through activation of G-protein-coupled metabotropic glutamate receptor 1 (mGluR1) leading to dephosphorylation of NMDAR GluN2B subunits, which decreases Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx to favor LTD over LTP, and cofilin, which promotes F-actin severing to destabilize dendritic spines. These findings reveal a novel interplay between NMDAR and mGluR1 signaling that converges on AKAP-anchored CaN to coordinate dephosphorylation of postsynaptic substrates linked to multiple aspects of A\u03b2-mediated synaptic dysfunction.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0675-24.2024","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T13:50:19Z","timestamp":1723470619000},"page":"e0675242024","source":"Crossref","is-referenced-by-count":17,"title":["Amyloid-\u03b2 Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling"],"prefix":"10.1523","volume":"44","author":[{"given":"Olga","family":"Prikhodko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-1730","authenticated-orcid":false,"given":"Ronald K.","family":"Freund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-3461","authenticated-orcid":false,"given":"Mark L.","family":"Dell\u2019Acqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"2025111207300586000_44.37.e0675242024.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1064-09.2009"},{"key":"2025111207300586000_44.37.e0675242024.2","doi-asserted-by":"publisher","DOI":"10.1523\/eneuro.0196-21.2021"},{"key":"2025111207300586000_44.37.e0675242024.3","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90086-7"},{"key":"2025111207300586000_44.37.e0675242024.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-22-09679.2002"},{"key":"2025111207300586000_44.37.e0675242024.5","doi-asserted-by":"crossref","first-page":"8140","DOI":"10.1016\/S0021-9258(19)83888-7","article-title":"Dephosphorylation of cAMP-dependent protein kinase regulatory subunit (type II) by calmodulin-dependent protein phosphatase. 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