title: Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice.
abstract: Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions.
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458.
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Orefice
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Chiu
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Tara A
authors.initials: TA
authors.lastname: LeGates
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Samer
authors.identifier: 0000-0002-3124-9525
authors.initials: S
authors.lastname: Hattar
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458.
authors.forename: Baoji
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218; rkuruvilla@jhu.edu.
authors.forename: Rejji
authors.initials: R
authors.lastname: Kuruvilla
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D017207:Rats, Sprague-Dawley; D014792:Visual Acuity; D000071818:Wnt-5a Protein / Q000235:genetics / Q000502:physiology*
chemical_list: D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse
keywords: adult hippocampus; autocrine Wnt signaling; dendrite arbors