In order to investigate this pathophysiology in a circuit-specific manner, and determine whether an α 5-PAM, MP-III-022, is able to reverse this, here we virally expressed two mutated human genes known to contribute to AD pathology, the Swedish (K670N, M671L), Florida (I716V), and London (V717I) mutations of human amyloid precursor protein (hAPP) and two mutations (M146L and L286V) of presenilin 1 (hPSEN1), specifically in the vHipp. This evidence concerns the gene APP and Alzheimer disease.