Alzheimer’s disease (AD) progresses with a deterioration of hippocampal function that is likely induced by amyloid beta (Aβ) 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 25–35) reduce sensory-induced theta oscillations. However, considering on the one hand that different Aβ sequences differentially affect hippocampal oscillations and on the other hand that Aβ 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 Aβ1–42 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 Aβ-treated animals responds to sensory stimulation (tail pinch) with an increase in lower frequencies. These findings demonstrate that Aβ alters induced theta rhythm, providing an in vivo model to test for therapeutic approaches to overcome Aβ-induced hippocampal and cognitive dysfunctions. 1. Introduction Alzheimer’s disease (AD), the most common form of dementia, is characterized by a progressive decline in cognitive function [1–5] that correlates with the extracellular accumulation of amyloid beta protein (Aβ) [1, 4, 5]. Deterioration of hippocampal function, likely induced by Aβ oligomers, contributes to the memory deficits associated with Alzheimer’s disease (AD) [5–8]. Normal hippocampal function is strongly dependent on a 3 to 10 Hz oscillatory activity, namely, the theta rhythm [9–11]. Theta oscillations have been associated with various cognitive processes in several species, including humans [9–11]. Theta rhythm abnormalities are usually related to memory deficits and pathological changes in the brain [12–14]. In fact, subjects with AD show a typical “electroencephalographic slowing” that includes increased slow rhythms and decreased fast rhythms [6, 13, 15, 16]. Regarding theta rhythm, AD patients show increased theta rhythm at rest [6, 15, 16], but they also show a decrease in induced-theta rhythm; both of these changes in theta rhythm correlate with a reduced cognitive performance [17]. A similar contradictory scenario has
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