THE CYCLIC-AMP SYSTEM AND DROSOPHILA LEARNING

The cyclic AMP (cAMP) system plays a critical role in olfactory learni ng in the fruit fly, Drosophila melanogaster, as evidenced by the foll owing: [1] The dunce gene encodes a form of cAMP phosphodiesterase (PD E). Flies carrying mutations at this gene show reduced PDE activity, h igh cAMP levels, and deficits in olfactory learning and memory [2]. Th e rutabaga gene encodes one type of adenylyl cyclase (AC) similar in p roperties to the Type I AC characterized from vertebrate brain. This e nzyme is activated by G-protein and Ca++ and has been postulated to be a molecular coincidence detector, capable of integrating information from two independent sources such as the conditioned stimulus (CS) and the unconditioned stimulus (US) delivered to animals during Pavlovian conditioning. Rutabaga mutant flies are deficient in AC activity and show behavioral defects similar to those exhibited by dunce mutants [3 ]. Flies carrying mutations in the gene (DCO) that encodes the catalyt ic subunit of protein kinase A (PKA), the major mediator of cAMP actio ns, show alterations in learning performance and a loss in PKA activit y. All three genes are expressed preferentially in mushroom bodies, ne uroanatomical sites that mediate olfactory learning. Interestingly, th e PDE and the catalytic subunit of PKA are found primarily in axonal a nd dendritic compartments of the mushroom body cells, whereas the AC i s found primarily in the axonal compartment. The reason for this diffe rential compartmentalization is unclear, although the hypothetical rol e of AC as coincidence detector would predict that CS and US stimuli a re integrated in the axonal compartment. These observations suggest th at cAMP is a dominant second messenger utilized by mushroom body cells to modulate their physiology while the animal is learning and consoli dating memory. However, many other types of molecules are likely invol ved in the physiological alterations that occur in these cells during learning, including cell surface proteins, transcription factors, and synaptic proteins.