Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain

Itaru Imayoshi; Masayuki Sakamoto; Toshiyuki Ohtsuka; Keizo Takao; Tsuyoshi Miyakawa; Masahiro Yamaguchi; Kensaku Mori; Toshio Ikeda; Shigeyoshi Itohara; Ryoichiro Kageyama

doi:10.1038/nn.2185

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.

Authors

Itaru Imayoshi¹, Masayuki Sakamoto, Toshiyuki Ohtsuka, Keizo Takao, Tsuyoshi Miyakawa, Masahiro Yamaguchi, Kensaku Mori, Toshio Ikeda, Shigeyoshi Itohara, Ryoichiro Kageyama

Affiliation

¹ Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.

PMID: 18758458
DOI: 10.1038/nn.2185

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