000175702 001__ 175702
000175702 005__ 20190316235327.0
000175702 0247_ $$2doi$$a10.1371/journal.pbio.1001262
000175702 02470 $$2ISI$$a000300951500008
000175702 037__ $$aARTICLE
000175702 245__ $$aFacilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement
000175702 269__ $$a2012
000175702 260__ $$c2012
000175702 336__ $$aJournal Articles
000175702 520__ $$aCell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM) that enhances spatial learning and memory in rats. We have now investigated the cellular and molecular basis of this cognitive enhancement, using biochemical, morphological, electrophysiological, and behavioral analyses. We have found that FGL triggers a long-lasting enhancement of synaptic transmission in hippocampal CA1 neurons. This effect is mediated by a facilitated synaptic delivery of AMPA receptors, which is accompanied by enhanced NMDA receptor-dependent long-term potentiation (LTP). Both LTP and cognitive enhancement are mediated by an initial PKC activation, which is followed by persistent CaMKII activation. These results provide a mechanistic link between facilitation of AMPA receptor synaptic delivery and improved hippocampal-dependent learning, induced by a pharmacological cognitive enhancer.
000175702 6531_ $$aCell-Adhesion Molecule
000175702 6531_ $$aLong-Term Potentiation
000175702 6531_ $$aProtein-Kinase-C
000175702 6531_ $$aGlutamate Receptors
000175702 6531_ $$aNmda Receptors
000175702 6531_ $$aSpatial Memory
000175702 6531_ $$aFgl-Peptide
000175702 6531_ $$aRat-Brain
000175702 6531_ $$aPlasticity
000175702 6531_ $$aInhibitor
000175702 700__ $$aKnafo, Shira
000175702 700__ $$aVenero, César
000175702 700__ $$aSánchez-Puelles, Cristina
000175702 700__ $$aPereda-Peréz, Inmaculada
000175702 700__ $$aFranco, Ana
000175702 700__ $$0243016$$aSandi, Carmen$$g160090
000175702 700__ $$aSuárez, Luz M.
000175702 700__ $$aSolís, José M.
000175702 700__ $$aAlonso-Nanclares, Lidia
000175702 700__ $$aMartín, Eduardo D.
000175702 700__ $$aMerino-Serrais, Paola
000175702 700__ $$aBorcel, Erika
000175702 700__ $$aLi, Shizhong
000175702 700__ $$aChen, Yongshuo
000175702 700__ $$aGonzalez-Soriano, Juncal
000175702 700__ $$aBerezin, Vladimir
000175702 700__ $$aBock, Elisabeth
000175702 700__ $$aDefelipe, Javier
000175702 700__ $$aEsteban, José A.
000175702 773__ $$j10$$k2$$qe1001262$$tPLoS Biol
000175702 8564_ $$s1403763$$uhttps://infoscience.epfl.ch/record/175702/files/Knafo_Facilitation%20of%20AMPA%20Receptor%20Synaptic.pdf$$yn/a$$zn/a
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000175702 937__ $$aEPFL-ARTICLE-175702
000175702 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000175702 980__ $$aARTICLE