An increase in neural stem cells and olfactory bulb adult neurogenesis improves discrimination of highly similar odorants

EMBO J. 2019 Mar 15;38(6):e98791. doi: 10.15252/embj.201798791. Epub 2019 Jan 14.

Abstract

Adult neurogenesis is involved in cognitive performance but studies that manipulated this process to improve brain function are scarce. Here, we characterized a genetic mouse model in which neural stem cells (NSC) of the subventricular zone (SVZ) were temporarily expanded by conditional expression of the cell cycle regulators Cdk4/cyclinD1, thus increasing neurogenesis. We found that supernumerary neurons matured and integrated in the olfactory bulb similarly to physiologically generated newborn neurons displaying a correct expression of molecular markers, morphology and electrophysiological activity. Olfactory performance upon increased neurogenesis was unchanged when mice were tested on relatively easy tasks using distinct odor stimuli. In contrast, intriguingly, increasing neurogenesis improved the discrimination ability of mice when challenged with a difficult task using mixtures of highly similar odorants. Together, our study provides a mammalian model to control the expansion of somatic stem cells that can in principle be applied to any tissue for basic research and models of therapy. By applying this to NSC of the SVZ, we highlighted the importance of adult neurogenesis to specifically improve performance in a challenging olfactory task.

Keywords: adult neurogenesis; neural stem cells; odor discrimination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin D1 / physiology
  • Cyclin-Dependent Kinase 4 / physiology
  • Discrimination Learning*
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Transgenic
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology*
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Odorants / analysis*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / physiology*

Substances

  • Ccnd1 protein, mouse
  • Cyclin D1
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4