In dendritic spines, SK channels are directly coupled to NMDA receptors. In addition to being activated by calcium flow through voltage-gated calcium channels, SK channels can be activated by calcium flowing through NMDA receptors, which occurs after depolarization of the postsynaptic membrane.  Experiments using apamin have shown that specifically blocking SK channels can increase learning and long-term potentiation. In addition, brain-derived neurotrophic factor (BDNF) causes the down-regulation of SK channels, which facilitates long-term potentiation. Increasing SK channel activity has the opposite effect and serves to impair learning. An increase in SK channel activity that occurs over time may be related to decreases in plasticity and memory that is seen with aging.