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

Nature Neuroscience volume 11, pages 1153–1161 (2008)Cite this article

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.

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Figure 1: Tamoxifen-induced Cre recombinase activity in adult NSCs in the SVZ of the lateral ventricles of Nes-CreERT2 mice.
Figure 2: Continuous adult neurogenesis in the olfactory bulb visualized by long-term labeling of NSCs.
Figure 3: Ablation of neurogenesis decreases the number of granule cells in the olfactory bulb.
Figure 4: Similar survival of early born granule cells in oil- and tamoxifen-treated Line 5-1/NSE-DTA mice.
Figure 5: Ablation of newly formed neurons does not affect discrimination and memory of odors.
Figure 6: Continuous adult neurogenesis in the dentate gyrus visualized by long-term labeling of NSCs.
Figure 7: Ablation of neurogenesis inhibits the increase of the granule cell number in the dentate gyrus.
Figure 8: Ablation of newly formed neurons impairs retention of spatial memory.

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Acknowledgements

We thank P. Soriano, F. Costantini and C. Lobe for materials, and K. Nakanishi, N. Tsunekawa, M. Hayashi, M. Fujioka, H. Kohda and K. Okamoto-Furuta for technical help. This work was supported by Grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. I.I. was supported by the 21st Century Center of Excellence Program of the Ministry of Education, Culture, Sports, Science and Technology of Japan and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

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Author notes

  1. Toshio Ikeda

    Present address: Present address: National Institute for Longevity Sciences, 36-3, Gengo, Morioka, Obu, Aichi 474-8511, Japan.,

Authors and Affiliations

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

    Itaru Imayoshi, Masayuki Sakamoto, Toshiyuki Ohtsuka & Ryoichiro Kageyama

  2. Kyoto University Graduate School of Biostudies, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan

    Itaru Imayoshi & Masayuki Sakamoto

  3. Japan Science and Technology Agency, CREST, Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507, Japan

    Itaru Imayoshi, Toshiyuki Ohtsuka & Ryoichiro Kageyama

  4. Kyoto University Graduate School of Medicine, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan

    Keizo Takao & Tsuyoshi Miyakawa

  5. Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Aichi, Japan

    Keizo Takao & Tsuyoshi Miyakawa

  6. Institute for Bioinformatics Research and Development and CREST, 4-1-8, Honcho, Kawaguchi, 332-0012, Saitama, Japan

    Keizo Takao & Tsuyoshi Miyakawa

  7. Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Masahiro Yamaguchi & Kensaku Mori

  8. RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan

    Toshio Ikeda & Shigeyoshi Itohara

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Contributions

I.I. conducted the experiments. I.I., M.S., M.Y. and K.M. carried out analysis on odorant discrimination and memory. I.I., K.T. and T.M. performed analysis on other behavioral tests. T.I. and S.I. provided the NSE-DTA mice. T.O. and R.K. supervised the project. I.I. and R.K. wrote the manuscript.

Corresponding author

Correspondence to Ryoichiro Kageyama.

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Imayoshi, I., Sakamoto, M., Ohtsuka, T. et al. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci 11, 1153–1161 (2008). https://doi.org/10.1038/nn.2185

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