Two pathways towards enhanced adult neurogenesis

Tashiro et al (2007) describe how mice exposed to an “enriched environment”, meaning larger cages with tunnels and running wheels, can have higher levels of neurogenesis than those without that exposure. That finding in itself is not new, but their team found that mice exposed to the enriched environment for just one week showed an increase in the number of newly differentiated neurons in the dentate gyrus.

They also looked for evidence of a “critical period” by placing the mice in the enriched cages either 1, 2, 3, or 4 weeks after the injection of BrdU, which stains differentiating neurons. The 1, 2, and 3 week enriched mice all had significantly more new neurons than control mice, but those enriched in the second week had the most new cells: the control had 12.5 +/- 0.6 cells per 106µm3; group 1 had ~ 22 +/2, group 2 had 27.9 +/- 3.7, and group 3 had ~18 +/-1 cells. The researchers determined that the majority of these new cells were the result of increased survival of differentiated neurons instead of increased proliferation. The density of the BrdU positive cells in group 2 was also significantly higher than that of any other. The authors suggest that the circuits formed at different times after neuron proliferation could correspond to specific experiences, which would allow for a time encoding of new memories.

Leuner et al describe a different pathway through which adult neurogenesis can increase: conditioned responses in a hippocampal-dependent stimulus learning tasks. Although the number of BrdU-labeled cells did not vary based on whether the mice were exposed to paired on unpaired stimuli, there was a significant and positive correlation between the number of conditioned responses the mice performed and the number of BrdU-labeled cells, r=0.65, p=0.03. The amount of new neurons dropped off slightly in number between 1 days to 30 days but there was no significant additional decline to 60 days, indicating that the increased neurogenesis is not transient.

The authors attempt to fit their data into the existing neurogenesis as increased learning paradigm, with some success. It is pretty clear that the better the animal learns (as measured by conditioned responses), the more the number of newly-born cells exist in the dentate gyrus, and based on the Tashiro’s evidence that is probably due to increased survival of neurons. Elucidating the role of neurogenesis in learning and memory is a theoretically important step for both enhancing normal human learning processes and understanding how and where the process fails.

References

Leuner B, Mendolia-Loffredo S, Kozorovitskiy Y, Samburg D, Gould E, Shors TJ. 2004 Learning enchances the survival of new neurons beyond the time when the hippocampus is required for memory. Journal of Neuroscience 24:7477-7481. doi:10.1523/JNEUROSCI.0204-04.2004.

Tashiro A, Makino H, Gage FH. 2007 Experience-specific functional modification of the dentate gyrus through adult neurogenesis: A critical period during an immature stage. Journal of Neuroscience 27:3252-3259. doi:10.1523/JNEUROSCI.4941-06.2007.