Our experiments suggest that the C-terminal domain of the GluN2B subunit is necessary and sufficient to produce memory enhancement, as long as it is coupled to Mg2+ dependent forms of GluN2 subunits such as GluN2A or GluN2B, while coupling of the GluN2A's C-terminal domain to GluN2B N-terminal and transmembrane domains lead to profound memory impairment. The gene discussed is GRIN2B; the disease is memory impairment.