S ome rats, and humans, are better than others at keeping their brains fresh and nimble with age. Hey-Kyoung Lee, Sun Seek Min, Michela Gallagher, and Alfredo Kirkwood (Johns Hopkins University, Baltimore, MD) now find that old rats stay smart by switching from one way of modifying synapses to another.

Gallagher has noted before that a subset of older rats maintain learning abilities equivalent to those of young rats. Learning involves the modification of synaptic strength: connections are strengthened via long-term potentiation (LTP) and weakened via long-term depression (LTD). When thinking of learning, says Kirkwood, “most people put the emphasis on LTP, but I have an appreciation for what makes things weaker.” When forming a new memory, “making [connections] stronger and making them weaker must be equally balanced.”

LTD comes in two flavors, one dependent on and another independent of NMDA receptors (NMDARs). The Baltimore group found that NMDAR-LTD declined with age, but there was no difference between old rats that were either smart or befuddled. But the old and smart rats showed far more non–NMDAR-LTD than either the young rats or the old and befuddled rats.

Thus it appears that some aging rats successfully switch from NMDAR-LTD to non–NMDAR-LTD. This switch is a smart strategy, because NMDAR-LTD can cause excitotoxicity, so decoupling from NMDARs with age “could be a way of managing excitotoxicity,” says Kirkwood. Once the non-NMDAR pathway is better characterized, it may make a better target than the NMDAR pathway for enhancing brain functioning in the elderly.


Lee, H.-K., et al. 2005. Nat. Neurosci. doi:.