When more is not more

oosting the function of a learning protein jams the brain with too much information, according to Ype Elgersma (Erasmus MC, Rotterdam, Netherlands), Alcino Silva (University of California, Los Angeles, CA), and colleagues. The result is a cautionary tale for those seeking to develop learning drugs. The team created mice lacking two inhibitory phosphorylation sites on CaMKII. Wild-type CaMKII is displaced from synapses in part by the phosphorylation, but the mutant protein has an enhanced affinity for synapses. This lowers the threshold for establishing long-term potentiation (LTP)—a synapsestrengthening event associated with learning—probably because it now takes less calcium rushing into the synapse to reach the necessary level of CaMKII activity. Initial water-maze learning by the mice was normal. But the mutant mice, unlike wild type, did not improve on their early learning. Silva believes that the mice solidify B