RYR3 is the channel gene that is most heavily supported by this data. RYR3 is a site at which calcium activated calcium efflux from sequestered intracellular stores elevates free cytoplasmic calcium levels. Brain RYR3 expression is highest in hippocampus [276, 277]. Significant evidence links RYRs to associative learning [278]. RYR3 knockout mice display alterations in several sorts of learning tasks [279]. Ryanodine and a number of other small molecule appear to provide excellent starting points for synthesis of selective RYR3 inhibitors [280].
