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1 Acta Neurobiologiae Experimentalis

1 2011

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The FORMIN 2 protein is required for the remodeling of consolidated memories

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Sananbenesi F. , Pinhero P. , Rebola N. , Kerimoglu C. , Burkhardt S. , Rizzoli S. , Mulle C. , Fischer A.

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The brain has a remarkable capacity to undergo plasticity changes that are believed to underlie the acquisition, consolidation and maintenance of memory traces. To identify the molecular and cellular substrates of cognitive function is a major aim of modern neuroscience. A critical mechanism that has been implicated with neuronal plasticity is the regulation of the actin cytoskeleton. Thus, we study the role of FORMIN 2 (FMN2), a protein that regulates actin dynamics, in the adult brain of mice. Fmn2-/- mice can normally form hippocampus-dependent associative and spatial memories but display a severe failure in adapting a once acquired memory. Thus, Fmn2-/- mice show dramatic impairments in reversal learning paradigms. On the molecular and cellular levels this phenotype is explained by deregulated actin dynamics in the hippocampal striatum lucidum linked to a reduced number of synaptic vesicles per active zone and led to specific changes in the physiology of mossy fiber-CA3 synapses. Our data indicates that FMN2 at the mossy fiber-CA3 synapse is required for the fine-tuning of hippocampal memory traces.