Dynamic interplay of frontoparietal cholinergic innervation and cortical reorganization in the regulation of attentional capacities in aging.

Cortical remodeling is linked to age-related cognitive changes in humans; however, the mechanisms underlying cortical reorganization in aging remain unknown. Here we examined the consequences of mild cholinergic thinning of the prefrontal cortex (PFC) and parietal cortex (PC) on attention performance-associated changes in cortical activity in young and aged rats. Prefrontal manipulation produced attentional deficits in aged but not young rats regardless of cholinergic pruning. Stereological assessment of c-fos expression revealed age-related reductions in occipital activity and a corresponding increase in PC activity, but these patterns did not correlate with performance. PC cholinergic deafferentation produced opposite changes in PFC recruitment between young and aged rats. Cholinergic pruning reversed the effects of PFC/PC cholinergic manipulations on the activity of CaMKII- and GAD-positive neurons in aged rats. Our results indicate that cortical shifts depend on multiple factors including chronological age, cholinergic changes, and cortical insult, and that cortical reorganization is not necessarily compensatory. Moreover, the cholinergic system modulates excitation/inhibition homeostasis to improve the efficiency of reorganized cortical circuits and stabilize attentional performance.