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The Journal of Neuroscience, April 28, 2004, 24(17):4197-4204; doi:10.1523/JNEUROSCI.0436-04.2004

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Development/Plasticity/Repair
A Synthetic Neural Cell Adhesion Molecule Mimetic Peptide Promotes Synaptogenesis, Enhances Presynaptic Function, and Facilitates Memory Consolidation

Karine Cambon,¹ Stine M. Hansen,² Cesar Venero,¹ A. Isabel Herrero,¹ Galina Skibo,² Vladimir Berezin,² Elisabeth Bock,² and Carmen Sandi^1,3

¹Psychobiology Department, Universidad Nacional de Educacion a Distancia, Ciudad Universitaria Sin Numero, 28040 Madrid, Spain, ²Protein Laboratory, Institute of Molecular Pathology, School of Medicine, University of Copenhagen, Panum Institute 6.2, DK-2200 Copenhagen N, Denmark, and ³Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland

The neural cell adhesion molecule (NCAM) plays a critical role in development and plasticity of the nervous system and is involved in the mechanisms of learning and memory. Here, we show that intracerebroventricular administration of the FG loop (FGL), a synthetic 15 amino acid peptide corresponding to the binding site of NCAM for the fibroblast growth factor receptor 1 (FGFR1), immediately after training rats in fear conditioning or water maze learning, induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced the presynaptic function through activation of FGFR1 and promoted synapse formation. These results provide the first evidence for a memory-facilitating effect resulting from a treatment that mimics NCAM function. They suggest that increased efficacy of synaptic transmission and formation of new synapses probably mediate the cognition-enhancing properties displayed by the peptide.

Key words: NCAM; mimetic peptide; synaptogenesis; synaptic plasticity; spatial learning; fear conditioning; rat

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Received Dec 1, 2003; revised March 7, 2004; accepted March 7, 2004.

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