News Release

Neuronal excitability may hold key to age-related decline in learning and memory

Peer-Reviewed Publication

Cell Press

By analyzing the effects of altered neuronal function in mice, researchers have gained new understanding of how changes in a particular neuronal characteristic, neuronal excitability, may negatively impact learning and memory as we age. The work is reported by Geoffrey Murphy and Alcino Silva and their colleagues at the University of California, Los Angeles.

Learning and memory impairments that arise independent of overt pathology are considered to be a normal component of aging. It is estimated that about 40% of people over the age of 65 years suffer from some sort of age-related cognitive decline. The exact cause of these age-related deficits in learning and memory is not currently known, but there have been numerous studies in the past that have implicated age-related changes in two neuronal attributes: a decrease in neuronal excitability, or the ability of neurons to be stimulated to fire, and age-related deficits in synaptic plasticity, or the ability of neurons to change some types of connections to other neurons. In the new study, funded by the National Institutes of Aging, researchers have established the link among neuronal excitability, synaptic plasticity, and aging.

Studying mice that had been genetically engineered to lack a particular ion channel auxiliary subunit, the researchers showed that the mice maintained enhanced neuronal excitability into old age, and, most importantly, that these mice exhibit a reduction in the threshold for the induction of specific forms of synaptic plasticity – in other words, these mice appear to change some kinds of inter-neuronal connections more readily than do normal mice of the same age. Furthermore, the aged mutant mice out-performed their age-matched wild-type littermates in the spatial version of the Morris water maze, a laboratory test for learning and memory.

Previous data suggested that in humans, the severity of age-related cognitive decline is affected by the genetic background of the individual. This was also the case for the genetically engineered mice. By manipulating the genetic background of the mice, the investigators were able to demonstrate that in some backgrounds the engineered mutation did not significantly increase neuronal excitability and that, in these cases, the mice did not exhibit the enhanced learning effect.

The new findings indicate that interactions between neuronal excitability and synaptic plasticity play a role in learning and that manipulations of either of these two parameters could be effective in ameliorating age-related cognitive decline.


Geoffrey G. Murphy, Nikolai B. Fedorov, K. Peter Giese, Masuo Ohno, Eugenia Friedman, Rachel Chen, and Alcino J. Silva: "Increased Neuronal Excitability, Synaptic Plasticity, and Learning in Aged Kvb1.1 Knockout Mice"

Publishing in Current Biology, Volume 14, Number 21, November 9, 2004, pages 1907–1915.

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