All animal procedures were approved by the Animal Care and Use Committee of Cleveland Clinic. Adult male Sprague–Dawley (250–300 g, 2–3 mo of age, Charles River) rats were used, and all experiments were performed during the light cycle. Tg-APPsw/PSEN1DE9 (APP/PS1, MMRRC Stock No: 41848-JAX), and C57BL/6 mice were purchased from Jackson Laboratory, regularly maintained and studied at six months old. Tg-APPsw/PSEN1DE9 mice were obtained as hemizygote by crossing the transgenics with animals on a C57BL/6 background. During experiment, non-transgenic littermates were used as the control for the transgenic mice with the same age (6 months old) and gender ratio (male/female ratio about 1). Metabotropic glutamate receptor 1 mutant mice (Grm1−/−, C57BL/6J-Grm1rcw−3J/GrsrJ, Jackson Laboratory stock No. 005521) crossed with APP/PS1 mice to generate the new strain (APP/PS1/Grm1−/−), which was validated by genotyping following the protocols provided by Jackson Laboratory. Experiments were conducted in mice at the age of 6 mo. The animals were randomly assigned to different groups with specific treatment, and another party blinded the experimenter to the individual groups. No statistical methods were used to predetermine sample sizes, but our sample sizes are similar to those reported in previous publications [30 (link),3 (link)].