Link between new neuron growth and environmental enrichment-facilitated behavioral effects questioned in new mouse study
By Jeffrey M. Perkel | May 1, 2006
Neurogenesis does not appear to be the reason why mice living in enriched environments tend to exhibit certain behavioral changes -- such as less anxiety -- relative to mice living in standard housing, according to a study published this week in Nature Neuroscience. The conclusion contradicts the recent hypothesis that neurogenesis in the dentate gyrus, a region of the hippocampus, is the cause of certain behavioral effects of environmental enrichment, which also include improved learning.
"This paper is very interesting," said Amelia Eisch, assistant professor of psychiatry at the University of Texas Southwestern Medical Center, who did not participate in the work. "It represents the next step in where the field of adult neurogenesis is going."
To date, the study of adult neurogenesis has largely been correlative, Eisch explained. Earlier research had demonstrated that environmental enrichment -- housing mice in larger, more complex environments -- leads both to increased neurogenesis in the dentate gyrus and to behavioral changes, including decreased anxiety and improved learning and memory. This study set out to test directly whether new neuron growth actually causes those behavioral changes, co-lead author Michael Drew, a postdoctoral fellow in Rene Hen's laboratory at Columbia University, told The Scientist.
The team used a targeted X-ray irradiation procedure to specifically abolish neurogenesis in the hippocampus, while leaving other areas of the brain intact. Then, after waiting two months for irradiation-induced inflammation to subside, the mice were split into two groups, one of which was housed in standard mouse cages, the other in enriched housing. Six weeks later, the mice were subjected to the Morris water maze, which tests spatial learning; to the novelty-suppressed feeding protocol, which measures anxiety; and to a test of habituation to new environments.
As expected, mice in enriched housing performed better in the spatial learning test, and also exhibited less anxiety-like behavior, said Drew. "We saw that, as other people had reported, enrichment had pretty big effects on their behavior." However, the authors were surprised to find that irradiation did not block the effects of enrichment, which argued against a role for neurogenesis in causing those effects.
"The hippocampus does many things, has many functions," said Eisch. "We don't know if adult neurogenesis is responsible for any of them. This paper shows that there's at least a few that neurogenesis is not responsible for."
An open question is how broadly applicable these results are. "It's certainly possible that there are other behaviors, or you could say psychological processes, that are affected by enrichment and that are neurogenesis-dependent," said Drew.
For instance, this study seems to contradict earlier findings that linked neurogenesis and enrichment-induced behavioral benefits. Serge Laroche, head of the laboratory of learning and memory at the University of Paris-South in Orsay, participated in one such study. Laroche told The Scientist that his study used different behavioral tests and different animals -- rats, rather than mice -- than does the current research. "In this field of research you can't generalize from one task to another task, because they probe different types of memory functions," he said. Laroche's study, published in 2005, tested the effect of neurogenesis on enrichment-facilitated long-term memory, as measured in the novel object recognition test. Perhaps, Laroche suggested, enrichment facilitates both learning and long-term memory, "but the mechanism of neurogenesis perhaps is only implicated in mediating the facilitation of memory, and not in mediating the facilitation of learning."
The study of adult neurogenesis is in the midst of a technical evolution, said Eisch, from anticancer drugs to whole-brain irradiation, to targeted irradiation in the current study. The next step in that evolution, researchers say, is the development of genetic tools, such as inducible transgenic mice, to manipulate neurogenesis in vivo, noninvasively and precisely. "Every approach gets us closer to figuring out what these new cells do, but the critical thing that is missing is a way to independently manipulate these cells. This is crucial," Eisch said.
Jeffrey M. Perkel
Links within this article
D. Meshi et al., "Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment," Nature Neuroscience, advance online publication, April 30, 2006.
R. Lewis, "The neurobiology of rehabilitation," The Scientist, June 30, 2003.
E. Bruel-Jungerman et al., "New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment," European Journal of Neuroscience, 2005.
K. Lee, "New neurons involved in memory formation," The Scientist, March 19, 2001.