Liu et al (Science, 304:1021-4) report that NMDA receptors containing NR2A and NR2B subunits are selectively coupled to long-term potentiation (LTP) and long-term depression (LTD) respectively. Because NR2B (but not NR2A) receptors occur outside synapses, and can be activated by glutamate spillover, this principle may underlie synaptic homeostasis.