Perhaps surprisingly, learning is not a uniquely human trait; not only do very simple animals learn, but most of what we know about the mechanisms of learning comes from studies of organisms like the sea hare (Aplysia)or the fruit fly (Drosophila). In both organisms, the cyclic AMP signalling pathway has been implicated; and in Drosophila, classic memory genes impact directly on the cAMP pathway: dunce encodes a cAMP-phosphodiesterase, and rutabaga an adenylate cyclase. For olfactory learning, in which flies are trained to associate a particular odour with a mild electric shock (and so avoid it), the memory trace has been localised to a tiny area in the middle of the brain, the `mushroom body'. In this paper, Gang Liu and colleagues trained flies to avoid certain shapes in their visual fields. They showed that a different area of the brain, the`fanlike body' is involved in shape recognition, and thus that there is no single, generic memory centre in the flies' brains. The technology to accomplish this experiment is remarkable: each fly was glued to a thin rod,attached to strain gauges that monitored the insect's flight. The fly was then placed in a panoramic flight simulator, shown various simple shapes, and was conditioned to fly so that they kept certain shapes out of the middle of their visual field in order to avoid an aversive stimulus (heat). Previous experiments showed that flies can recognise separately at least five different parameters; size, colour, elevation in the panorama, vertical compactness and contour orientation.
To test which region of the brain was responsible for shape memory the team designed transgenic flies where they could inhibit memory formation in specific regions of the brain by expressing tetanus toxin (CntE), a specific inhibitor of synaptobrevin (an essential synaptic protein), before conditioning the insects to avoid certain stimuli and testing their recall. By blocking memory formation in specific locations in the intact brain, the team found that the mushroom body had nothing to do with this learning task;instead the largest region of the central complex, the `fanlike body' needed to be working for memory formation.
Of course, the presence of tetanus toxin might have induced some developmental deficit, rather than directly impacting on learning. So the authors used a new Drosophila trick. Gal80ts is a protein that binds to GAL4 and inhibits it, but releases GAL4 at higher temperatures(>30°C), allowing the expression of genes controlled by GAL4. By constructing mutant flies expressing the tetanus toxin under the control of GAL4, but in the presence of the Gal80ts inhibitor, the team were able to prevent expression of the gene at normal temperatures, confirming that presence of the gene did not affect the flies' memory formation. But as soon as the temperature rose the flies began expressing tetanus toxin and showed exactly the same learning deficits, so tetanus toxin was impacting on the learning process itself.
The authors then repeated the experiments with mutant flies lacking rutabaga (adenylate cyclase) that can fly and navigate, but cannot learn. By adding back normal rutabaga function, they showed that cAMP signalling is indeed required in the fanlike body for learning to take place.
As a final flourish, the authors were able to show that two different visual discriminations (an elevation of the whole panorama cf. orientation of the training shapes) could be associated with two distinct subsets of cells within the fanlike body. The results thus showed that while cAMP is a general property of learning, different regions of the brain are responsible for different memory modalities.
