Loss of medial septal modulation of dentate gyrus physiology in young mice overexpressing human beta-amyloid precursor protein

Abstract

Mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show deficits in hippocampal-dependent spatial learning and hippocampal short- and long-term plasticity at ages preceding Abeta plaque deposition. We determined whether young PDAPP mice also exhibit alterations in septohippocampal function in vivo, which plays an important role in cognitive function. Electrical stimulation of the medial septum significantly increased neuronal excitability and reduced paired-pulse facilitation in the dentate gyrus. Medial septal-induced facilitation of dentate neuronal excitability was reduced in PDAPP mice. The inhibitory effects of medial septum stimulation on dentate paired-pulse facilitation were also attenuated in PDAPP mice. Young mice overexpressing hbetaAPP exhibit early abnormalities in neural circuits implicated in cognitive function that may play an important role in the more profound deficits observed in aged PDAPP mice.