A major mystery of many types of neurological and psychiatric disorders,
such as Alzheimers disease (AD), remains the underlying, disease-specific
neuronal damage. Because of the strong interconnectivity of neurons in the
brain, neuronal dysfunction necessarily disrupts neuronal circuits. In this
article, we review evidence for the disruption of large-scale networks from
imaging studies of humans and relate it to studies of cellular dysfunction
in mouse models of AD. The emerging picture is that some forms of early
network dysfunctions can be explained by excessively increased levels of
neuronal activity. The notion of such neuronal hyperactivity receives strong
support from in vivo and in vitro cellular imaging and electrophysiological
recordings in the mouse, which provide mechanistic insights underlying the
change in neuronal excitability. Overall, some key aspects of AD-related neuronal dysfunctions
in humans and mice are strikingly similar and support the continuation of such a translational
strategy.