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Valentin Stein"Regulation of synapse number and plasticity by syncam 1-mediated synaptic adhesion"

Abstract :

Synaptogenesis is required to wire neuronal circuits in the developing brain, and remodels adult circuits during learning. Synaptic connectivity may be organized by trans-synaptic adhesion and signaling molecules, such as neuroligins, SynCAMs, and EphB receptors. However, the roles of cell adhesion in guiding synapse formation and remodeling in vivo remain incompletely understood. We now demonstrate that the elevated expression of SynCAM 1, a synaptogenic adhesion molecule of the immunoglobulin superfamily, increases the number of excitatory synapses in transgenic mice. The continued elevation of SynCAM 1 is required to sustain this effect. Conversely, SynCAM 1 knock-out mice exhibit reduced excitatory synapse numbers. Moreover, overexpression of SynCAM 1 decreases long-term depression, a measure for synaptic plasticity, and abrogates spatial learning, whereas SynCAM 1 loss increases long-term depression and promotes learning. Thus, SynCAM 1-mediated synaptic adhesion physiologically regulates synapse number and plasticity, which contributes to the wiring of neuronal circuits and affects behavior.

Selected publications

Pfeffer CK, Stein V, Keating DJ, Maier H, Rinke I, Rudhard Y, Hentschke M, Rune GM, Jentsch TJ, Hübner CA (2009) NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. J Neurosci 29:3419-30
Mank M, Santos AF, Direnberger S, Mrsic-Flogel TD, Hofer SB, Stein V, Hendel T, Reiff DF, Levelt C, Borst A, Bonhoeffer T, Hubener M, Griesbeck O (2008) A genetically encoded calcium indicator for chronic in vivo two-photon imaging. Nat Methods 5:805-811
Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, Klein R, Acker-Palmer A (2008): Serine phosphorylation of ephrinB2 regualtes trafficking of synaptic AMPA receptors. Nat Neurosci 11:1035-43