Neuronal basis of age-related working memory decline

Normal ageing results in the decline of higher cognitive functions, such as working memory and the ability to concentrate. A connection between the neurochemical environment and neuronal function in the prefrontal cortex (PFC) has been proposed as a key factor modulating these declines. Recordings from PFC neurons in young, middle-aged and older monkeys during a learning task reveal a significant decline in persistent firing in the aged PFC neurons that are responsible for maintaining the signal in working memory during a delay following a cue. This firing level can be rescued by restoring an optimal neurochemical environment, present at younger ages, through inhibition of cyclic AMP signalling and closure of the potassium channels that weaken network connectivity. These findings suggest potential therapeutic targets for cognitive enhancers in humans.