We identified several potential synaptic substrates of cognitive dysfunction associated with aging. These include an imbalance towards inhibition, exaggerated synaptic activity and impaired cholinergic input in different areas of the neocortex. The findings suggest that intervention aimed at balancing, rather than just enhancing synaptic activity may be a viable therapeutic strategy to improve cognitive function in unsuccessful aging or in Alzheimer’s disease (Bories C, et al., PLoS One 7: e46111; Bories C, et al., J Neurosci 33:1344-1356).