Hippocampal Neurogenesis is not Required for Behavioral Effects of Environmental Enrichment

While hippocampal granule cell neurogenesis is now well established in primates, including humans, the function of the newly generated cells remains less well established. One of the best studied models of neurogenesis involves housing rodents in a behaviorally enriched environment, a type of Club Med for rats and mice. The animals are exposed to improved stimuli in the environment such as toys, increased exercise, and in some cases more diverse diet. In comparison to standard rodent housing, enriched environment living results in increased neurogenesis in rats and mice. Because enrichment of the environment also improves spatial learning and memory, it has been speculated that increased neurogenesis directly results in improved spatial learning and memory.

A recent study out of the Hen lab at Columbia University provides evidence that factors other than neurogenesis are responsible for the behavioral improvements induced by living in an enriched environment. This work, co-authored by Meshi, et al. from New York and Paris, published in Nature Neuroscience (9:729–731, 2006), used a focal irradiation strategy to block neurogenesis in the hippocampus of mice subsequently housed in enriched and standard housing environments. The investigators found that focal X-irradiation blocked the increased neurogenesis normally induced by an enriched environment. However, despite this irradiation impairment of neurogenesis, housing in an enriched environment still improved spatial learning and decreased anxiety-like behavior in mice.

This study is important because it highlights the need to establish causal relationships between the presence of neurogenesis in the mammalian brain, and the function of the newly generated cells. While exercise, antidepressant medications, and other physiological, pharmacological, and pathological stimuli can all increase neurogenesis, the functional consequences of these alterations still need to be unraveled. Whether there are differences between neurogenesis in humans in response to physiological stimuli such as exercise and pathological stimuli such as ischemia or seizures is unknown. At the experimental model level, there is some evidence that seizure induced neurogenesis may be proepileptic. Newly generated granule cells following acute seizures have been shown to aberrantly migrate to the dentate hilus, where they form aberrant, synchronous connections with CA3 neurons.

While the findings of this study need to be confirmed in higher mammals, they also provide initial evidence that focal irradiation to the hippocampal area can potentially be delivered in a spatial memory sparing fashion. This finding has particular relevance to the ongoing multicenter trial using gamma knife radiosurgery as an alternative strategy to mesial temporal lobe resection for temporal lobe epilepsy. It is intriguing to consider that focal radiation may potentially be able to spare some of the spatial memory impairment known to occur after dominant temporal lobe surgical resections for epilepsy.

GUY M. MCKHANN II, M.D.

EPILEPSY RESEARCH