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. The gene discussed is PSEN1; the disease is Alzheimer disease.