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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 stronger and making them weaker must be equally balanced."
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. c6 n+ h0 L6 L4 z, }& g& [* xLTD 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. m6 {& p7 }! Q, z7 g( F
. ^' N/ z# s! ]& VThus 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.: ~ g& f4 B+ L1 Y4 `+ J
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A9 \5 u3 S* L: L) c$ b$ e" BLee, H.-K., et al. 2005. Nat. Neurosci. doi:10.1038/nn1586.(S ome rats, and humans, are better than ) |
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