Reduced growth cone motility in cultured neurons from Drosophila memory mutants with a defective cAMP cascade.

Drosophila memory mutants dunce (dnc) and rutabaga (rut) are known to have altered intracellular cAMP levels, nerve terminal growth, and plasticity of synaptic transmission. Because the growth cone is responsible for neurite outgrowth and synaptogenesis, video microscopy was used to examine growth cone morphology and behavior of mutant neurons in larval CNS cultures. We found that growth cone exploratory movement was nearly arrested by both mutations, even though they change cAMP levels in opposite directions. The dnc phenotype could be mimicked by normal neurons when perfused with dibutyryl cAMP (db-cAMP) or forskolin. In contrast, rut growth cones became active when perfused with db-cAMP. Furthermore, motility was also restored by counterbalancing the effects of the two genes in double mutants, indicating that dynamic control of growth cone motility in developing Drosophila neurons requires optimal cAMP levels within an operational range. These findings represent the first demonstration of altered growth cone properties in learning and memory mutants and establish in a natural setting the role of cAMP in growth cone motility and neuronal plasticity.