However, repetitive or continuous heat-shock treatments rescue the developmental phenotype. Thus, the learning defect can be rescued by acute expression of the NF1 transgene during adulthood, but the developmental defect requires repetitive or continuous heat-shock treatment during development. The learning scores of all three mutant genotypes are very similar. Sustained expression of this PKA subunit rescues the small body size phenotype of NF1 mutants. For undertraining, flies were subjected to 3 repeats of electric shock in a single training trial instead of 12 trials.
Biochemical assays provide direct evidence to support the idea.
AC activity has been examined in membrane fractions of adult brain tissues. However, significant GTPgammaS-stimulated activity occurs above the basal level in the mutants. Overexpression of NF1 in control flies does not increase AC activity, whereas the reduction in stimulated AC activity seen in NF1 mutants is mostly rescued by acutely induced expression of the NF1 transgene, indicating that NF1 is indeed able to regulate cAMP synthesis. Together, these results reveal a new mechanism that describes how G-proteins activate the cAMP pathway for normal learning and memory. Therefore, NF1 may be important for coordinating activities of multiple signal-transduction pathways.