Enhanced learning after genetic overexpression of a brain growth protein

Aryeh Routtenberg*, Isabel Cantallops, Sal Zaffuto, Peter Serrano, Uk Namgung

*Corresponding author for this work

Research output: Contribution to journalArticle

170 Scopus citations

Abstract

Ramon y Cajal proposed 100 years ago that memory formation requires the growth of nerve cell processes. One-half century later, Hebb suggested that growth of presynaptic axons and postsynaptic dendrites consequent to coactivity in these synaptic elements was essential for such information storage. In the past 25 years, candidate growth genes have been implicated in learning processes, but it has not been demonstrated that they in fact enhance them. Here, we show that genetic overexpression of the growth- associated protein GAP-43, the axonal protein kinase C substrate, dramatically enhanced learning and long-term potentiation in transgenic mice. If the overexpressed GAP-43 was mutated by a Ser → Ala substitution to preclude its phosphorylation by protein kinase C, then no learning enhancement was found. These findings provide evidence that a growth-related gene regulates learning and memory and suggest an unheralded target, the GAP- 43 phosphorylation site, for enhancing cognitive ability.

Original languageEnglish (US)
Pages (from-to)7657-7662
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number13
DOIs
StatePublished - Jun 20 2000

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