Mental retardation in humans is caused by various factors, including mutations in single genes. Many of these genes have orthologues in the fruit fly Drosophila melanogaster, and Didelot et al. have shown that one of these is crucial for the formation of long-term memory.

Tequila (TEQ) is a serine protease in the fly, and is the orthologue of human neurotrypsin. Mutations in neurotrypsin can lead to 'non-syndromic' mental retardation (where there are no apparent defects in neural development and no other symptoms). The authors therefore investigated whether TEQ is involved in long-term memory in the fly.

The type of memory they tested is called 'odour avoidance'. Flies are repeatedly exposed to two odours. One odour is always accompanied by an electric shock, so that the flies learn to avoid it. Repeated training sessions with rests in between them lead to long-term memory formation, which requires protein synthesis, whereas continuous 'massed training' leads to the formation of a type of memory that does not require new proteins to be made.

Flies carrying a mutation in the teq gene that reduces TEQ expression showed a reduced ability to form long-term memories, although their performance after massed training and on short-term memory tests was normal. This pattern of memory defect also occurred in flies in which RNA interference was used to suppress teq expression specifically in the mushroom bodies, which are crucial for olfactory learning and memory.

But these results do not tell us whether the effects of the TEQ mutation result from defects in the process of memory formation in the adult or from abnormal development of the neural systems that are required for olfactory long-term memory. To address this question, the authors used an inducible system to turn teq expression on or off in the mushroom bodies at specific times. When teq expression was suppressed in the mushroom bodies of adult flies, they developed a strong defect in long-term memory, which was restored when teq expression was allowed to resume.

These data, together with evidence that teq mRNA is upregulated in the mushroom bodies after long-term memory training, support the idea that TEQ has a crucial role in the formation of long-term memories in the fly. It is possible that neurotrypsin has a similar function in humans, but more work will be needed to clarify just what that function is.