Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction.  The prefrontal cortex is involved in working memory, which “holds” information through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. In this study, the authors studied the neuronal activity of PFC neurons in aged monkeys. They found marked loss of PFC persistent firing with advancing age. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings suggest possible neurochemical treatments for age-related changes in PFC circuits.

Wang M et al., Neuronal basis of age-related working memory decline.         Nature 476: 210–213 (2011).

http://www.nature.com/nature/journal/v476/n7359/full/nature10243.html