Accumulation of amyloid plaques comprises one of the major hallmarks of Alzheimer's disease (AD). In rodents, acute treatment with amyloid-beta (A beta; 1-42) elicits immediate debilitating effects on hippocampal long-term potentiation (LIP). Whereas LIP contributes to synaptic information storage, information is transferred across neurons by means of neuronal oscillations. Furthermore, changes in theta-gamma oscillations, that appear during high-frequency stimulation (HFS) to induce LIP, predict whether successful LIP will occur. Here, we explored if intra-cerebral treatment with A beta(1-42), that prevents LIP, also results in alterations of hippocampal oscillations that occur during HFS of the perforant path-dentate gyrus synapse in 6-month-old behaving rats. HFS resulted in LIP that lasted for over 24 h. In A beta-treated animals, LIP was significantly prevented. During HFS, spectral power for oscillations below 100 Hz (delta, theta, alpha, beta and gamma) was significantly higher in A beta-treated animals compared to controls. In addition, the trough-to-peak amplitudes of theta and gamma cycles were higher during HFS in A beta-treated animals. We also observed a lower amount of envelope-to-signal correlations during HFS in A beta-treated animals. Overall, the characteristic profile of theta gamma oscillations that accompany successful LIP induction was disrupted. These data indicate that alterations in network oscillations accompany A beta-effects on hippocampal LTP. This may comprise an underlying mechanism through which disturbances in synaptic information storage and hippocampus-dependent memory occurs in AD.
