Age-related increase of sI_AHP in prefrontal pyramidal cells of monkeys: relationship to cognition

Abstract 

Reduced excitability, due to an increase in the slow afterhyperpolarization (and its underlying current sI_AHP), occurs in CA1 pyramidal cells in aged cognitively-impaired, but not cognitively-unimpaired, rodents. We sought to determine whether similar age-related changes in the sI_AHP occur in pyramidal cells in the rhesus monkey dorsolateral prefrontal cortex (dlPFC). Whole-cell patch-clamp recordings were obtained from layer 3 and layer 5 pyramidal cells in dlPFC slices prepared from young (9.6 ± 0.7 years old) and aged (22.3 ± 0.7 years old) behaviorally characterized subjects. The amplitude of the sI_AHP was significantly greater in layer 3 (but not layer 5) cells from aged-impaired compared with both aged-unimpaired and young monkeys, which did not differ. Aged layer 3, but not layer 5, cells exhibited significantly increased action potential firing rates, but there was no relationship between sI_AHP and firing rate. Thus, in monkey dlPFC layer 3 cells, an increase in sI_AHP is associated with age-related cognitive decline; however, this increase is not associated with a reduction in excitability.

Keywords: Slice, Patch-clamp, Voltage-clamp, Potassium channels, Excitability