Work with Drosophila learning mutants has yielded insights on the biochemical mechanism underlying learning and memory. Of the six learning-deficient mutants isolated to date, four show well defined alterations in monoamine transmitter metabolism, or in cyclic AMP metabolism. In general, mutations which affect monoamines tend primarily to effect learning acqusition; while those which affect cAMP metabolism tend to affect short term memory retention after training. For two mutations that affect learning - dunce and Dopa decarboxylase - the primary metabolic lesions has been identified using gene-dosage studies and temperature-sensitive alleles. This needs to be done with our other mutants with well defined biochemical effects - turnip (affects serotonin receptor binding activity); rutabaga (affects calcium-activated adenylate cyclase) and radish (affects protein phosphorylation). We will try to do this (i) by orthodox biochemical experiments on the relevant metabolic lesions; (ii) by better genetic mapping to ensure that the biochemical lesions co-map with the learning defect; (iii) by gene-dosage studies and (iv) by isolating new mutant alleles, including temperature-sensitive ones. Using segmental-aneuploid screens, we will also try to map and obtain mutants in other proteins on the learning-related metabolic pathway - in three monoamine synthetic enzymes, in the Ns protein, and in cAMP dependent protein kinase. We will continue our work on the larval heart, which appears to alter its beat rate by the same serotonin-cAMP system implicated in learning. We will also continue our behavioral work, seeking to refine the correlation between biochemistry and behavior for temperature-sensitive dunce and rutabaga mutants.
