Figure 7.

Changes in DNC regulation with advancing age weaken synaptic efficacy and contribute to reductions in the persistent dlPFC Delay cell firing underlying working memory. A. Deep layer III neuropil in the dlPFC of a young (9yo) vs. an aged (29yo) monkey. White and green circles mark unlabeled and α2A-AR-labeled dendritic spines, respectively. Please note that spine density for both categories decreases with age. The reduction in α2A-AR-labeling is consistent with autoradiographic measures of reduced α2A-AR expression in the aged monkey dlPFC (Bigham and Lidow, 1995; Moore et al., 2005). B. The persistent firing of dlPFC Delay cells during a spatial working memory task markedly declines with advancing age. Blue=firing for the neurons’ preferred direction; dark red=firing for the neurons’ nonpreferred direction. From (Wang et al., 2011a). C. The persistent firing of aged dlPFC neurons was significantly increased by iontophoresis of the α2A-AR agonist, guanfacine, which inhibits cAMP signaling. Adapted from (Wang et al., 2011a). D. A schematic representation of some of the changes in DNC signaling in layer III spines with advancing age that lead to disinhibition of Ca⁺²-cAMP signaling. See text for detailed description.