Motor protein KIF1A is essential for hippocampal synaptogenesis and learning enhancement in an enriched environment

Neuron. 2012 Feb 23;73(4):743-57. doi: 10.1016/j.neuron.2011.12.020.

Abstract

Environmental enrichment causes a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) plays an important role in enrichment-induced neuronal changes; however, the precise mechanism underlying these effects remains uncertain. In this study, a specific upregulation of kinesin superfamily motor protein 1A (KIF1A) was observed in the hippocampi of mice kept in an enriched environment and, in hippocampal neurons in vitro, BDNF increased the levels of KIF1A and of KIF1A-mediated cargo transport. Analysis of Bdnf(+/-) and Kif1a(+/-) mice revealed that a lack of KIF1A upregulation resulted in a loss of enrichment-induced hippocampal synaptogenesis and learning enhancement. Meanwhile, KIF1A overexpression promoted synaptogenesis via the formation of presynaptic boutons. These findings demonstrate that KIF1A is indispensable for BDNF-mediated hippocampal synaptogenesis and learning enhancement induced by enrichment. This is a new molecular motor-mediated presynaptic mechanism underlying experience-dependent neuroplasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Astrocytes / physiology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cells, Cultured
  • Conditioning, Psychological / physiology
  • Disks Large Homolog 4 Protein
  • Environment*
  • Fear / physiology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Green Fluorescent Proteins / genetics
  • Guanylate Kinases / metabolism
  • Hippocampus / cytology*
  • Kinesin / deficiency
  • Kinesin / metabolism*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neurons / physiology*
  • RNA, Messenger / metabolism
  • Synaptophysin / metabolism
  • Transfection / methods

Substances

  • Brain-Derived Neurotrophic Factor
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Kif1a protein, mouse
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • RNA, Messenger
  • Synaptophysin
  • Green Fluorescent Proteins
  • Guanylate Kinases
  • Kinesin