Amyloid Beta Peptides Differentially Affect Hippocampal Theta Rhythms<i>In Vitro</i>

Resumen

Soluble amyloid beta peptide (A β ) is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble A β alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different A β peptides, we also compared A β 25 − 35 and A β 1 − 42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μ M). We found that A β 25 − 35 reduces, with less potency than A β 1 − 42 , carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of A β 25 − 35 but was reduced by A β 1 − 42 . Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of exerting a generalized inhibitory effect on neuronal network function.