Molecular Basis of Plasticity: SynCAM 1 Adhesion Dynamically Regulates Synapse Number and Impacts Plasticity and Learning

Neurons that fire together wire together.
Adhesion molecule SynCAM1: promotes new synapses in the developing brain, holds synaptic junctions together, and impacts the maintenance and function of these structure.

Elissa M. Robbins, Alexander J. Krupp, Karen Perez de Arce, Ananda K. Ghosh, Adam I. Fogel, Antony Boucard, Thomas C. Südhof, Valentin Stein, Thomas Biederer

Summary

Synaptogenesis is required for wiring neuronal circuits in the developing brain and continues to remodel adult networks. However, the molecules organizing synapse development and maintenance in vivo remain incompletely understood. We now demonstrate that the immunoglobulin adhesion molecule SynCAM 1 dynamically alters synapse number and plasticity. Overexpression of SynCAM 1 in transgenic mice promotes excitatory synapse number, while loss of SynCAM 1 results in fewer excitatory synapses. By turning off SynCAM 1 overexpression in transgenic brains, we show that it maintains the newly induced synapses. SynCAM 1 also functions at mature synapses to alter their plasticity by regulating long-term depression. Consistent with these effects on neuronal connectivity, SynCAM 1 expression affects spatial learning, with knock-out mice learning better. The reciprocal effects of increased SynCAM 1 expression and loss reveal that this adhesion molecule contributes to the regulation of synapse number and plasticity, and impacts how neuronal networks undergo activity-dependent changes.

SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones.
Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7568-73. Epub 2010 Apr 5.
Stagi M, Fogel AI, Biederer T.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.

Abstract
Neuronal growth cones are highly motile structures that tip developing neurites and explore their surroundings before axo-dendritic contact and synaptogenesis. However, the membrane proteins organizing these processes remain insufficiently understood. Here we identify that the synaptic cell adhesion molecule 1 (SynCAM 1), an immunoglobulin superfamily member, is already expressed in developing neurons and localizes to their growth cones. Upon interaction of growth cones with target neurites, SynCAM 1 rapidly assembles at these contacts to form stable adhesive clusters. Synaptic markers can also be detected at these sites. Addressing the functions of SynCAM 1 in growth cones preceding contact, we determine that it is required and sufficient to restrict the number of active filopodia. Further, SynCAM 1 negatively regulates the morphological complexity of migrating growth cones. Focal adhesion kinase, a binding partner of SynCAM 1, is implicated in its morphogenetic activities. These results reveal that SynCAM 1 acts in developing neurons to shape migrating growth cones and contributes to the adhesive differentiation of their axo-dendritic contacts.

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