Drosophila can learn in several associative conditioning paradigms. Flies carrying the mutation dunce were selected for their poor performance in one such task, a negative reinforcement olfactory conditioning paradigm (Dudai et al., 1976). dunce flies express two other mutant phenotypes, female sterility, and reduced activity for one of the two cyclic AMP phosphodiesterases present in normal flies, PDE II (Byers et al., 1981) . . The experiments described below indicate that the normal dunce gene (dunce+) probably codes for PDE II itself, rather than for a regulator that affects PDE II and possibly other activities.
A micro-assay technique is described that allows the separate measurement of PDE I and PDE II when both are present in mixture. PDE II is shown to occur at high specific activity in the nervous system, which is consistent with a role for this enzyme in neuronal function. The phenotype of female sterility associated with dunce mutants can be suppressed by any of three suppressor mutations. These do not suppress the other two phenotypes of reduced PDE II activity and poor learning, indicating that these phenotypes are closer to the primary defect associated with dunce mutants. Reduced PDE II activity correlates with poor learning in dunce flies in all three developmental stages that were tested (first and third instar larvae, and adults), as well as in response to genetic modifications of dunce gene activity. The results of several biochemical and genetic experiments fail to reveal any abnormal regulation of PDE II activity in dunce flies. In Drosophila, as a rule, the activity level of an enzyme correlates linearly with the activity of the enzyme's structural gene. The specific activity of PDE II is shown to correlate in a one to one fashion with the level of normal dunce gene activity at five different doses of dunce+.
Taken as a whole, these experiments provide strong support for the hypothesis that PDE II represents the primary product of the dunce gene, indicating a role for this enzyme in the learning of Drosophila.
