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[BSI Seminar Series (BSS)] Professor Kaoru Inokuchi, University of Toyama

“ Functional Roles of Adult Neurogenesis in Learning and Memory ”

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March 09, 2012 16:00 - 17:30


BSI Central Building 1F Seminar Room


Functional Roles of Adult Neurogenesis in Learning and Memory
Kaoru Inokuchi
Department of Biochemistry, Graduate School of Medicine & Pharmaceutical Sciences, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan,

In the adult brain, new neurons are continuously produced in the subgranular zone of the hippocampal dentate gyrus. New neurons are synaptically integrated into neuronal circuitry of the dentate gyrus as excitatory granule cells. A growing body of evidence indicates that adult neurogenesis is involved in the modulation of certain types of hippocampus-dependent memory. In this seminar, I will discuss a novel role the new neurons play in the information processing in the hippocampus and the reciprocal aspect of neural plasticity-mediated regulation of neurogenesis.
Acquired memory initially depends on the hippocampus for the process of cortical permanent memory formation. The mechanisms through which memory becomes progressively independent from the hippocampus remain unknown. Using two mouse models in which hippocampal neurogenesis is physically or genetically suppressed, we show that decreased neurogenesis is accompanied by a prolonged HPC-dependent period of associative fear memory. Inversely, enhanced neurogenesis by voluntary exercise sped up the decay rate of hippocampus-dependency of memory, without loss of memory. Consistently, decreased neurogenesis facilitated the long-lasting maintenance of rat hippocampal long-term potentiation in vivo. Therefore, the level of hippocampal neurogenesis plays a role in determination of the hippocampus-dependent period of memory in adult rodents.

A substantial fraction of newly generated neurons die before they mature, and the survival rate of new neurons are regulated in an experience-dependent manner. Previous study showed that high-frequency stimulation (HFS) of perforant path fibers to the hippocampal dentate gyrus induces the long-term potentiation (LTP) in the dentate gyrus, and enhances the survival of newly generated neurons in the dentate gyrus. We addressed whether a time period exists during which the survival of new neurons is maximally sensitive to the HFS. We found that the enhancement of cell survival by HFS was exclusively restricted to the specific narrow period during immature stages of new neurons (7-10 days after birth). These results suggest that the LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in rat dentate gyrus. We finally addressed how neural plasticity regulates the integration pattern of new neurons into preexisting circuits. We found that neural plasticity differentially regulates the integration of new neurons into the activated circuit, dependent on their developmental stage. Consequently, new neurons at different developmental stages may play distinct roles in processing the acquired information by modulating the connectivity of activated circuits via their integration.

1. Kitamura, T., Saitoh, Y., Takashima, N., Murayama, A., Niibori, Y., Ageta, H., Sekiguchi, M., Sugiyama, H. & Inokuchi, K. Cell 139, 814-827 (2009).
2. Okada, D., Ozawa, F. & Inokuchi, K. Science, 324, 904-909 (2009).
3. Kitamura T., Saitoh Y., Murayama A., Sugiyama H., and Inokuchi K. Mol. Brain 3, 13 (2010).
4. Inokuchi K. Curr Opin Neurobiol, 21, 360-364 (2011).
5. Kitamura T., Okubo-Suzuki R., Takashima N., Murayama A., Hino T., Nishizono H., Kida S., and Inokuchi K. Mol Brain, 5, 5 (2012).

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Open to Public
Toshihiko Hosoya [Toshihiko Hosoya, Local Neuronal Circuits ]
Name: Seminar Committee
Phone: 048-462-1111 (Ext. 7518)