Roles of Continuous Neurogenesis in the Structural and Functional Integrity of the Adult Forebrain

Nat Neurosci. 2008 Oct;11(10):1153-61. doi: 10.1038/nn.2185. Epub 2008 Aug 31.

Abstract

Neurogenesis occurs continuously in the forebrain of adult mammals, but the functional importance of adult neurogenesis is still unclear. Here, using a genetic labeling method in adult mice, we found that continuous neurogenesis results in the replacement of the majority of granule neurons in the olfactory bulb and a substantial addition of granule neurons to the hippocampal dentate gyrus. Genetic ablation of newly formed neurons in adult mice led to a gradual decrease in the number of granule cells in the olfactory bulb, inhibition of increases in the granule cell number in the dentate gyrus and impairment of behaviors in contextual and spatial memory, which are known to depend on hippocampus. These results suggest that continuous neurogenesis is required for the maintenance and reorganization of the whole interneuron system in the olfactory bulb, the modulation and refinement of the existing neuronal circuits in the dentate gyrus and the normal behaviors involved in hippocampal-dependent memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult Stem Cells / physiology*
  • Animals
  • Antigens, CD / metabolism
  • Behavior, Animal / drug effects
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Proliferation*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / injuries
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Enzyme Activation / drug effects
  • Glycoproteins / metabolism
  • Integrases / genetics
  • Integrases / metabolism
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Memory / drug effects
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neurons / cytology
  • Neurons / physiology*
  • Odorants
  • Olfactory Bulb / cytology
  • Olfactory Bulb / injuries
  • Peptides / metabolism
  • Prosencephalon / physiology*
  • Tamoxifen / pharmacology

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Peptides
  • Tamoxifen
  • Cre recombinase
  • Integrases
  • Bromodeoxyuridine