Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement

被引：40

作者：

Knafo, Shira ^{[1
,2
,3
]}

Venero, Cesar ^{[4
]}

Sanchez-Puelles, Cristina ^{[1
]}

Pereda-Perez, Inmaculada ^{[4
]}

Franco, Ana ^{[5
]}

Sandi, Carmen ^{[6
]}

Suarez, Luz M. ^{[2
,3
,7
]}

Solis, Jose M. ^{[7
]}

Alonso-Nanclares, Lidia ^{[2
,3
]}

Martin, Eduardo D. ^{[8
]}

Merino-Serrais, Paula ^{[2
,3
]}

Borcel, Erika ^{[4
]}

Li, Shizhong ^{[9
]}

Chen, Yongshuo ^{[9
]}

Gonzalez-Soriano, Juncal ^{[10
]}

Berezin, Vladimir ^{[9
]}

Bock, Elisabeth ^{[9
]}

DeFelipe, Javier ^{[2
,3
]}

Esteban, Jose A. ^{[1
]}

机构：

[1] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, Madrid, Spain

[2] Univ Politecn Madrid, CSIC, Inst Cajal, Ctr Tecnol Biomed, Madrid, Spain

[3] CIBERNED, Madrid, Spain

[4] Univ Nacl Educ Distancia, Dept Psychobiol, E-28040 Madrid, Spain

[5] Univ Autonoma Madrid, Ctr Nacl Biotecnol, CSIC, Madrid, Spain

[6] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland

[7] Hosp Ramon & Cajal, Serv Neurobiol Invest, IRYCIS, E-28034 Madrid, Spain

[8] Univ Castilla La Mancha, Dept Ciencias Med, Albacete, Spain

[9] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, Prot Lab, Copenhagen, Denmark

[10] Univ Complutense, Fac Vet Med, Dept Anat, E-28040 Madrid, Spain

来源：

PLOS BIOLOGY | 2012年 / 10卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

CELL-ADHESION MOLECULE; LONG-TERM POTENTIATION; PROTEIN-KINASE-C; GLUTAMATE RECEPTORS; NMDA RECEPTORS; SPATIAL MEMORY; FGL-PEPTIDE; RAT-BRAIN; PLASTICITY; INHIBITOR;

D O I：

10.1371/journal.pbio.1001262

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：17

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