Editors' ChoiceNeuroscience

Brings Back Memories

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Science Translational Medicine  24 Aug 2011:
Vol. 3, Issue 97, pp. 97ec137
DOI: 10.1126/scitranslmed.3003066

The prefrontal cortex is a hallmark of human intelligence. It analyzes sensory information and plans and executes complex actions on time scales that range from seconds to years. These cognitive functions rely on a core prefrontal cortex function, working memory (WM), which allows the brain to hold information temporarily for processing. Unfortunately, this advanced cortical area is also exquisitely sensitive to normal aging, and memory decline can adversely affect an individual’s life. Now, Wang et al. unveil the neuronal basis of such age-related decline in WM and shed light on new treatments to reduce or even reverse these debilitating changes.

The authors first examined the effect of aging on neuronal activity in the prefrontal cortex across three groups of monkeys: young, middle-aged, and aged, with two animals in each group. The monkeys were trained to perform a simple WM task, in which they had to remember the spatial location of a visual cue over the WM period (2.5 s). Microelectrodes were inserted into the prefrontal cortex to record neuronal activities. As expected from known prefrontal cortex physiology, a large number of prefrontal cortex neurons showed WM-related activity; that is, the neurons fired persistently and carried relevant information during the period in which the animal had to keep the spatial location of the visual cue in mind. The Wang et al. study showed that there was an age-related decline, not only in general prefrontal cortex neuronal activity but also in the difference in neuronal activity for different spatial-location information. Thus, the individual’s ability to accurately hold information in prefrontal cortex neurons declines as the monkey ages.

Furthermore, when the authors injected into the prefrontal cortex minute amount of chemical agents that blocked the cyclic adenosine 5´-monophosphate signaling pathway, which normally inhibits WM, prefrontal cortex neuronal activity was restored in aged monkeys to a level comparable with that of younger monkeys. This study reveals a promising target for new medications designed to correct age-related WM deficits. The authors are now conducting a clinical trial to translate their findings to use in patients.

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

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