title: Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses.
abstract: Growing evidence indicates that Wingless-type (Wnt) signaling plays an important role in the maturation of the central nervous system. We report here that Wingless-type family member 5A (Wnt-5a) is expressed early in development and stimulates dendrite spine morphogenesis, inducing de novo formation of spines and increasing the size of the preexisting ones in hippocampal neurons. Wnt-5a increased intracellular calcium concentration in dendritic processes and the amplitude of NMDA spontaneous miniature currents. Acute application of Wnt-5a increased the amplitude of field excitatory postsynaptic potentials (fEPSP) in hippocampal slices, an effect that was prevented by calcium-channel blockers. The physiological relevance of our findings is supported by studies showing that Wnt scavengers decreased spine density, miniature excitatory postsynaptic currents, and fEPSP amplitude. We conclude that Wnt-5a stimulates different aspects of synaptic differentiation and plasticity in the mammalian central nervous system.
authors.affiliation: Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
authors.forename: Lorena
authors.initials: L
authors.lastname: Varela-Nallar
authors.forename: Iván E
authors.initials: IE
authors.lastname: Alfaro
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Serrano
authors.forename: Jorge
authors.initials: J
authors.lastname: Parodi
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003712:Dendrites; D049229:Dendritic Spines; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D016202:N-Methylaspartate; D009473:Neuronal Plasticity; D009474:Neurons / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure*; D051153:Wnt Proteins / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D018698:Glutamic Acid; D016202:N-Methylaspartate