Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage - PubMed (original) (raw)

Comparative Study

Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage

Ayumu Tashiro et al. J Neurosci. 2007.

Abstract

Neural circuits in the dentate gyrus are continuously modified by adult neurogenesis, whose level is affected by the animal's experience. However, it is not known whether this experience-dependent anatomical modification alters the functional properties of the dentate gyrus. Here, using the expression of immediate early gene products, c-fos and Zif268, as indicators of recently activated neurons, we show that previous exposure to an enriched environment increases the total number of new neurons and the number of new neurons responding to reexposure to the same environment. The increase in the density of activated new neurons occurred specifically in response to exposure to the same environment but not to a different experience. Furthermore, we found that these experience-specific modifications are affected exclusively by previous exposure around the second week after neuronal birth but not later than 3 weeks. Thus, the animal's experience within a critical period during an immature stage of new neurons determines the survival and population response of the new neurons and may affect later neural representation of the experience in the dentate gyrus. This experience-specific functional modification through adult neurogenesis could be a mechanism by which new neurons exert a long-term influence on the function of the dentate gyrus related to learning and memory.

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Figures

Figure 1.

Figure 1.

The enriched environment and examined sections from the dentate gyrus. a, A picture of the enriched cage used in this study. b, Representative images of sections used for the analysis from anterior (#1) to posterior (#8). The sections were immunostained with anti-NeuN antibody. Scale bar, 100 μm.

Figure 2.

Figure 2.

One week preexposure to an enriched environment soon after neuronal birth increases the number of new neurons. a, Timeline of BrdU injections and exposure to an enriched environment. b, Representative images of BrdU-stained dentate sections from the control group and group 2. Scale bar, 100 μm. c, Density of BrdU+/NeuN+ and BrdU+/NeuN− cells. d, Estimated density of BrdU+/NeuN+ cells in the suprapyramidal and infrapyramidal blades of each level along the anteroposterior axis. Section numbers correspond to the numbers in Figure 1_b_. *p < 0.05, **p < 0.005, ***p < 0.0005 by Fisher's LSD test.

Figure 3.

Figure 3.

One week preexposure to an enriched environment soon after neuronal birth increases the number of new neurons responding to reexposure to the same environment. a, Confocal images of dentate granule cell layer triple immunostained with BrdU (green), c-fos (red), and NeuN (blue). Arrows indicate triple-positive cells. Scale bar, 50 μm. b, Density of BrdU+/NeuN+/c-fos+ cells in mice exposed to an enriched environment immediately before being perfused. c, Proportions of c-fos+ in BrdU+/NeuN+ cells. d, Proportions of c-fos+ in NeuN+ cells. **p < 0.005 by Fisher's LSD test.

Figure 4.

Figure 4.

Experience-specific increase in the number of activated new neurons. a, Experimental timeline. b, Confocal images of dentate granule cell layer triple immunostained with BrdU, Zif268, and NeuN. Arrows indicate triple-positive cells. Scale bar, 50 μm. Density of BrdU+/NeuN+ cells (c) and of BrdU+/NeuN+/Zif268+ cells (d) in each group. Proportions of Zif268+ in BrdU+/NeuN+ cells (e) and in NeuN+ cells (f) in each group. **p < 0. 005, ***p < 0.0005 by Fisher's LSD test.

Figure 5.

Figure 5.

Long-term survival of mature new neurons does not require continuous exposure to the environment that rescued the new neurons during the critical period. a, Experimental timeline. b, Density of BrdU+/NeuN+ cells in each group.

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