This seizure susceptibility in young 3xTg-AD mice was reduced by passive immunization with an anti-human APP/Aβ antibody or by mGluR5 blockade suggesting a role of intraneuronal human APP/Aβ prior to extracellular amyloid deposition and mGluR5 activation in exaggerated seizure susceptibility in these mice. The gene discussed is GRM5; the disease is Alzheimer disease.