Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice

Chih Ming Chen, Lauren L. Orefice, Shu-Ling Chiu, Tara A. LeGates, Samer Hattar, Richard L Huganir, Haiqing Zhao, Baoji Xu, Rejji Kuruvilla

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)E619-E628
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number4
DOIs
StatePublished - Jan 24 2017

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Dendrites
Maintenance
Hippocampus
Brain
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neuronal Plasticity
Pyramidal Cells
Glutamate Receptors
Neurodegenerative Diseases
Cognition
Spine
Neurons
Spatial Learning
Spatial Memory

Keywords

  • Adult hippocampus
  • Autocrine Wnt signaling
  • Dendrite arbors

ASJC Scopus subject areas

  • General

Cite this

Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice. / Chen, Chih Ming; Orefice, Lauren L.; Chiu, Shu-Ling; LeGates, Tara A.; Hattar, Samer; Huganir, Richard L; Zhao, Haiqing; Xu, Baoji; Kuruvilla, Rejji.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 4, 24.01.2017, p. E619-E628.

Research output: Contribution to journalArticle

Chen, Chih Ming ; Orefice, Lauren L. ; Chiu, Shu-Ling ; LeGates, Tara A. ; Hattar, Samer ; Huganir, Richard L ; Zhao, Haiqing ; Xu, Baoji ; Kuruvilla, Rejji. / Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 4. pp. E619-E628.
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