01 May 2003

Counterintuitive as it may seem, in tomorrow's Science researchers report that the inhibitory neurotransmitter ã-aminobutyric acid (GABA) can temporarily restore age-related losses of visual acuity in monkeys.

Audie Leventhal, University of Utah, Salt Lake City, together with colleagues in Hefei and Kunming, China, tested GABA, and its agonists and antagonists, on neurons in area VI of the visual cortex. These neurons respond to specific orientations and direction of motion of objects in the visual field, but their function declines with age, which may explain why older animals perform poorly in visual tests.

Leventhal had previously reported that area VI neurons in very old monkeys (26 to 30 years old) have decreased signal-to-noise ratios and poorly discern orientation and directional movement. They are also much more likely to fire spontaneously, suggesting that their inhibitory modulation is defective. In this study, the authors tested individual area VI neurons from both old and young animals. When the researchers measured electrical activity in untreated neurons from old animals, the cells responded equally well to stimuli from any orientation, suggesting they had lost directional selectivity, whereas young neurons responded only to stimuli in specific locations of the visual field. By contrast, when Leventhal added GABA to the old neurons, they regained directional selectivity within minutes. Moreover, they improved their signal-to-noise ratio and reduced spontaneous firing, approaching levels typical of their young counterparts. The GABA agonist muscimol elicited an even better signal-to-noise ratio than did GABA. The neurons reverted to their original performance equally rapidly after drug withdrawal.

The GABA antagonist bicuculline reversed the effect of GABA on old neurons, and it abolished directional selectivity in young neurons. The latter finding suggests that there may be a basal level of GABA activity in area VI that is absent in older cortices. GABA and muscimol had strong effects on older neurons, reducing spontaneous firing by 58 and 83 percent, respectively, vs. reductions in young neurons of only 11 and 9 percent, respectively.

While this research was limited strictly to individual neurons in the visual cortex, its implications may be broad and "important for the treatment of the sensory, motor, and cognitive declines that accompany old age," according to the authors.—Tom Fagan