Changes in electrophysiological properties of prefrontal cortical pyramidal neurons with normal aging and age-related cognitive decline

Declines in executive function occur with normal aging. In vivo single and multiple unit recordings have established that changes in sustained action potential firing rates of prefrontal cortex (PFC) pyramidal cells underlie the successful performance of cognitive tasks. PFC pyramidal cells exhibit age-related changes in morphology that likely affect neuronal physiology. Hence, age-related cognitive deficits may result from electrophysiological changes in these cells that, in turn, could alter the firing properties of these cells. To address this issue, whole-cell voltage and current clamp recordings were used to compare the electrophysiological properties of both layer 2/3 and layer 5 cells in in vitro PFC slices in young (≤ 13 years old) versus aged (≥ 19 years old) behaviorally characterized monkeys. Cells from aged animals exhibited decreased spontaneous excitatory postsynaptic current frequencies and increased spontaneous inhibitory postsynaptic current frequencies, while showing no changes in miniature postsynaptic events. In addition, age-related increases in slow afterhyperpolarization amplitudes were observed. The most dramatic finding was that layer 2/3 cell excitability (i.e. AP firing rate) was increased with age. This increased AP firing rates was correlated with age-related increases in input resistance. In contrast, no such AP firing rate or input resistance increases was observed in layer 5 cells. The lack of firing rate alterations with age in layer 5 is consistent with past studies suggesting that behaviors dependent on the striatum (a primary target of layer 5 pyramidal cells) are spared in senescence. In the aged group, significant U-shaped relationships were found between layer 2/3 firing rate and performance on PFC dependent tasks such that firing rates that were too low or too high are associated with impaired behavioral performance. We suggest that firing rates that are too low are insufficient to contrast relevant from background stimuli, and firing rates that are too high may result in increased "noise," disrupting cognitive performance. However, no relationship between firing rate and cognitive performance was found in the young group. These results are consistent with the hypothesis that altered AP firing rates in layer 2/3 pyramidal cells underlie age-related declines in executive functions mediated by the PFC.