Ablation of BAF170 in Developing and Postnatal Dentate Gyrus Affects Neural Stem Cell Proliferation, Differentiation, and Learning

Mol Neurobiol. 2017 Aug;54(6):4618-4635. doi: 10.1007/s12035-016-9948-5. Epub 2016 Jul 8.

Abstract

The BAF chromatin remodeling complex plays an essential role in brain development. However its function in postnatal neurogenesis in hippocampus is still unknown. Here, we show that in postnatal dentate gyrus (DG), the BAF170 subunit of the complex is expressed in radial glial-like (RGL) progenitors and in cell types involved in subsequent steps of adult neurogenesis including mature astrocytes. Conditional deletion of BAF170 during cortical late neurogenesis as well as during adult brain neurogenesis depletes the pool of RGL cells in DG, and promotes terminal astrocyte differentiation. These derangements are accompanied by distinct behavioral deficits, as reflected by an impaired accuracy of place responding in the Morris water maze test, during both hidden platform as well as reversal learning. Inducible deletion of BAF170 in DG during adult brain neurogenesis resulted in mild spatial learning deficits, having a more pronounced effect on spatial learning during the reversal test. These findings demonstrate involvement of BAF170-dependent chromatin remodeling in hippocampal neurogenesis and cognition and suggest a specific role of adult neurogenesis in DG in adaptive behavior.

Keywords: Adult neuronal stem cells neurogenesis; Astrogenesis; BAF170; Hippocampus; Learning and memory; SWI/SNF complex.

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation* / drug effects
  • Cell Proliferation / drug effects
  • Chromosomal Proteins, Non-Histone / deficiency*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / growth & development*
  • Integrases / metabolism
  • Maze Learning / drug effects
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nestin / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Neurogenesis / drug effects
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Spatial Learning* / drug effects
  • Tamoxifen / pharmacology
  • Transcription Factors

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nestin
  • Smarcc2 protein, mouse
  • Transcription Factors
  • Tamoxifen
  • Cre recombinase
  • Integrases