21 Feb 2000

Memory deficits due to NMDA receptor loss in the hippocampus can be overcome by enriched environments, according to a report from Joe Tsien and his Princeton colleagues in the March issue of Nature Neuroscience. Tsien and others had previously demonstrated that NMDA (N-methyl-D-aspartate) receptors for the neurotransmitter glutamate in the CA1 region of the hippocampus are critical for long-term potentiation (LTP), a strong candidate for the physiological process that creates memories for storage. Correlated with these results are findings that mice lacking NMDA receptors in CA1 have severely impaired spatial learning and memory.

In the current paper, Tsien and his coauthors show that mice whose CA1 NMDA receptors have been selectively knocked out also have deficits in nonspatial memory formation such as object recognition, olfactory discrimination, and contextual fear memories. However, when exposed to an enriched environment (new toys, running wheels, etc., introduced every other day) as young adults (age 1.5 to two months), they somehow overcome their CA1 NMDA receptor deficits. For some tests, they tested as well as control mice who had the same stimulating experiences, but in all cases, they tested significantly better than littermates who had only spent time in the unenriched environment of a plain mouse cage. In parallel experiments, the researchers showed that this recuperation correlated with increased synapse formation in CA1, though they are careful to stress that this does not mean these synaptic changes underlie the effects on memory.

They do, however, conclude that, "Our data indicate that CA1 NMDA receptor activity is critical in hippocampus-dependent nonspatial memory, but is not essential for experience-induced synaptic structural changes." These findings may be interesting in light of the theory that increased years of education may create "reserve neural capacity" that protects individuals against the risk of Alzheimer's disease.—Hakon Heimer

(See also a related News and Views article by Howard Eichenbaum and Kristen Harris of Boston University in the same issue.)