Abstract

The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (θ) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid β (Aβ) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Aβ injections progressively impaired behavioral performances, the associated hippocampal θ power, and θ frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the θ rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Aβ treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.