Amyloid beta peptide slows down sensory-induced hippocampal oscillations

Abstract

Alzheimers disease (AD) progresses with a deterioration of hippocampal function that is likely induced by amyloid beta (A) oligomers. Hippocampal function is strongly dependent on theta rhythm, and disruptions in this rhythm have been related to the reduction of cognitive performance in AD. Accordingly, both AD patients and AD-transgenic mice show an increase in theta rhythm at rest but a reduction in cognitive-induced theta rhythm. We have previously found that monomers of the short sequence of Aβ (peptide 2535) reduce sensory-induced theta oscillations. However, considering on the one hand that different A sequences differentially affect hippocampal oscillations and on the other hand that A oligomers seem to be responsible for the cognitive decline observed in AD, here we aimed to explore the effect of Aβ oligomers on sensory-induced theta rhythm. Our results show that intracisternal injection of A142 oligomers, which has no significant effect on spontaneous hippocampal activity, disrupts the induction of theta rhythm upon sensory stimulation. Instead of increasing the power in the theta band, the hippocampus of A-treated animals responds to sensory stimulation (tail pinch) with an increase in lower frequencies. These findings demonstrate that A alters induced theta rhythm, providing an in vivo model to test for therapeutic approaches to overcome A-induced hippocampal and cognitive dysfunctions. Copyright © 2012 Fernando Pea-Ortega and Ramn Bernal-Pedraza.