Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner

Abstract

Soluble amyloid beta (Abeta) oligomers might trigger early cognitive impairment in Alzheimer's Disease (AD) through the impairment of proper neuronal network function. We have recently shown that the short sequence Abeta(25-35) affects the spontaneous activity in hippocampal slices, when was added to the bath, at high nanomolar concentrations. In the present study, we aimed to characterize the effects of the oligomerized full length sequence Abeta(1-42) on the spontaneous network activity in the CA1 hippocampal area testing whether such effects are age dependent. By performing extracellular field recordings of spontaneous network activity of hippocampal slices, we found that an oligomerized solution of Abeta(1-42) (osAbeta) potently inhibit, in a dose-dependent manner, the spontaneous hippocampal network activity with an IC(50) of 0.4 +/- 3.2 nM and a maximal effect reached around 10 nM. While spontaneous hippocampal network activity is unaffected by age, the sensitivity of spontaneous hippocampal network activity to osAbeta (10 nM) appears to be increased in slices from older animals. Moreover, to see a significant reduction in spontaneous network activity in slices from animals in their second week of life 100nM osAbeta was needed. The osAbeta-induced reduction in hippocampal network activity is accompanied by a presynaptic reduction in both spontaneous and miniature synaptic potentials. Finally, we demonstrated that the effect produced by osAbeta on spontaneous network activity was specific, reversible and unrelated with cell death. In conclusion, our data show that osAbeta alters hippocampal network activity at concentrations commonly observed in AD patients and that such effect of osAbeta increase with age.