Figure 4.

Prefrontal ACh release and choline clearance capacity assessed using choline-sensitive microelectrodes and fixed-potential amperometry in vivo. Representative traces depicting choline spikes following brief depolarizing pulses of potassium in the medial PFC of young (A) and aged (B) rats that received chronic i.c.v. infusions of either oligomeric Aβ or control peptide. These signals reflect ACh release and occur as a consequence of rapid hydrolysis of ACh by acetylcholinesterase. The hydrolyzed choline is oxidized by the enzyme choline oxidase present on the platinum recording site at a fixed potential to generate increases in current. (C) Depolarization-evoked cholinergic signal amplitudes were lower in aged as well as Aβ-infused rats. Examples of current traces illustrate the effects of either Aβ oligomers or control peptide on clearance kinetics of exogenously applied choline in young (D) and aged (E) rats. Choline uptake rates were calculated from the hemicholinium-sensitive component of the clearance curve that accounts for the decrease in choline concentration from 40% to 80% of the peak amplitudes. (F) The capacity to clear choline from the extracellular space declined in soluble Aβ-infused rats and this effect was more prominent in aged animals (refer statistical analysis from 2 × 2 ANOVA in results). Data are Mean ± SEM. Aβ (−) depict chronic infusions with the control peptide while Aβ (+) indicate animals infused with soluble Aβ in (C) and (F), respectively.