Human ageing is associated with a decline in visual function that is proposed to result from the degeneration and/or dysfunction of central visual pathways. But the precise nature of the changes in cortical function that accompany ageing remains obscure. In a paper published in Science, Leventhal et al. show that a shortage of GABA (γ-aminobutyric acid)-mediated inhibition in the visual cortex might underlie age-related visual deficits.

Senescent humans suffer from a number of disturbances of vision, including decreased visual acuity and motion sensitivity. The orientation- and direction-selective responses of cells in the primary visual cortex (area V1) participate in the perception of form and motion. Leventhal and co-workers have previously shown that V1 neurons in old monkeys lack orientation and direction selectivity. In their latest study, Leventhal et al. tested the hypothesis that a loss of GABA inhibition contributes to age-related changes in the responses of V1 cells.

In old monkeys, the electrophoretic application of GABA or muscimol, a GABAA receptor receptor agonist, increased the proportion of cells that showed significant orientation or direction selectivity. GABA agonists were less effective in young monkeys, in which cells were already strongly selective. In young animals, the GABAA receptor antagonist bicuculline markedly diminished selectivity; however, this antagonist had little effect on the already low percentage of selective cells in old animals. GABA and muscimol both reduced the peak visual response and the spontaneous electrical activity of V1 cells, and increased the signal-to-noise ratio of these neurons; these effects were more pronounced in old monkeys. By contrast, bicuculline markedly impaired the ability of neurons to signal visual stimuli in young monkeys, but had relatively little effect on the neuronal responses of senescent animals.

These results indicate that GABA-mediated inhibition in the visual cortex degrades with age, possibly because GABA production is reduced in older animals. If reduced inhibition underlies age-related functional defects in widespread cortical regions, the GABA system could represent an important target for the treatment of sensory, motor and cognitive deficits that emerge as we grow old.