DEFECTIVE LEARNING IN MUTANTS OF THE DROSOPHILA GENE FOR A REGULATORYSUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE

Disruptions of a Drosophila gene encoding a regulatory subunit of cAMP -dependent protein kinase homologous to mammalian RI beta (dPKA-RI) we re targeted to the first (noncoding) exon of dPKA-RI via site-selected P element mutagenesis. Flies homozygous for either of two mutant alle les showed specific defects in olfactory learning but not in subsequen t memory decay. In contrast, olfactory acuity and shock reactivity, co mponent behaviors required for normal odor avoidance learning, were no rmal in these mutants. Northern and Western blot analyses of mRNA and protein extracted from adult heads have revealed a complex lesion of t he PKA-RI locus, including expression of a novel product and over-or u nderexpression of wild-type products in mutants. Western blot analysis revealed reductions in RI protein in mutants. PKA activity in the abs ence of exogenous cAMP also was significantly higher than normal in ho mogenates from mutant adult heads. These two mutant alleles failed to complement each other for each of these phenotypic defects, eliminatin g second-site mutations as a possible explanation. These results estab lish a role for an RI regulatory subunit of PKA in Pavlovian olfactory conditioning.