Facilitation of ampa receptor synaptic delivery as a molecular mechanism for cognitive enhancement

Shira Knafo, César Venero, Cristina Sánchez-Puelles, Inmaculada Pereda-Peréz, Ana Franco, Carmen Sandi, Luz M. Suárez, José M. Solís, Lidia Alonso-Nanclares, Eduardo D. Martín, Paula Merino-Serrais, Erika Borcel, Shizhong Li, Yongshuo Chen, Juncal Gonzalez-Soriano, Vladimir Berezin, Elisabeth Bock, Javier DeFelipe, José A. Esteban

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Cell 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.

Original languageEnglish
Article numbere1001262
JournalPLoS Biology
Volume10
Issue number2
DOIs
StatePublished - 1 Feb 2012
Externally publishedYes

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