title: SynCAM 1 adhesion dynamically regulates synapse number and impacts plasticity and learning.
abstract: 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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Robbins
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Krupp
authors.forename: Karen
authors.initials: K
authors.lastname: Perez de Arce
authors.forename: Ananda K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Adam I
authors.initials: AI
authors.lastname: Fogel
authors.forename: Antony
authors.initials: A
authors.lastname: Boucard
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Valentin
authors.initials: V
authors.lastname: Stein
authors.forename: Thomas
authors.initials: T
authors.lastname: Biederer
mesh_terms: D000818:Animals; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D013037:Spatial Behavior; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins