Mutations in the dopa decarboxylase gene affect learning in Drosophila.

Abstract

Fruit flies synthesize several monoamine neurotransmitters. Dopa decarboxylase (Ddc) mutations affect synthesis of two of these, dopamine and serotonin. Both transmitters are implicated in vertebrate and invertebrate learning. Therefore, we bred flies of various Ddc genotypes and tested their learning ability in positively and negatively reinforced learning tasks. Mutations in the Ddc gene diminished learning acquisition approximately in proportion to their effect on enzymatic activity. Courtship and mating sequences of the mutants appeared normal, except for one aspect of male courtship that had previously been shown to be experience dependent. In contrast, the effect on behavior patterns that do not involve learning-phototaxis, geotaxis, olfactory acuity, responsiveness to sucrose-was relatively slight under these conditions. Moderate Ddc mutations affected the acquisition of learned responses while leaving memory retention unaltered. This is in contrast to the mutations dunce, rutabaga, and amnesiac, which primarily affect short-term memory.Biogenic monoamines (principally dopamine, serotonin, epinephrine, and norepinephrine in vertebrates; dopamine, serotonin, and octopamine in invertebrates) are a group of neurotransmitters formed from aromatic amino acids that seem to be related in their physiological and behavioral functions. Monoamines are implicated in synaptic modulation in a variety of animals (1-4). Numerous pharmacological studies in vertebrates indirectly but consistently suggest a role for monoamines in attentiveness and behavioral plasticity (5), particularly a role for dopamine in positively reinforced learning (6). In line with this, some neurophysiological and behavioral experiments suggest an involvement of norepinephrine in experience-dependent changes during a critical period of visual cortical development (7, 8; B. Gordon, J. Moran, P. Trombley, and J. Soyke, personal communication).In invertebrates, there is specific neurophysiological evidence that serotonin is involved in sensitization and classical conditioning of the siphon-withdrawal reflex in Aplysia (9-11). Serotonin, applied to the relevant synapses in the circuit, can mimic behavioral sensitization, producing facilitation of synaptic transmission in the reflex pathway. The behavioral effect of sensitizing stimuli can be blocked by cinanserine, a moderately specific antagonist of serotonin (9).Recently, however, this story has been complicated by a failure to find serotonin-like immunoreactivity in identified facilitatory neurons [those of the L29 group (12)], although serotonergic terminals from other cells are found in the relevant synaptic sites (12).In both vertebrates and invertebrates, therefore, the evidence linking biogenic monoamines to learning is cumulatively suggestive, but it is in no case unassailable. We decided to investigate this relation further, using Drosophila mutants.Wright and his colleagues (13,14,15) MATERIALS AND METHODSCulture Conditions, Fly Stocks, and Crosses. All Drosophila stocks were bred ...

Genetics and genomics of Drosophila mating behavior

“…The Fast and Slow replicate lines were significantly diverged from Generation 25. We analyzed the mating speed data from generations [25][26][27][28][29] …”

“…These include mutations in genes required for normal morphology [white (13,14), yellow (14), and curved (15)], as well as genes involved in learning and memory [Calcium calmodulin kinase II (16), dunce (17,18), rutabaga (19,20), turnip (19,21), and amnesiac (20,22,23)], circadian rhythm [period (18,(24)(25)(26)] and dopamine and serotonin synthesis [Dopa decarboxylase (27), pale (28,29), tan (30,31), and ebony (32)(33)(34)], sex determination [doublesex (35)(36)(37), transformer (38)(39)(40)(41)(42)(43), fruitless (44)(45)(46)(47), and sex lethal (48)], pheromone production [desaturase 2 (49)], and accessory gland-specific peptides (6-8, 50-52). a subset of loci identified by mutational analysis, or will the analysis of natural variants reveal novel loci?…”

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

“…Similarly, agonists could be designed that couple the DopR99B receptor to one or another of the two second messenger pathways that it potentially can activate. Such compounds could lead to the development of highly effective insect control agents, given the preferential expression of this Drosophila dopamine receptor in mushroom bodies (Han et al, 1996) and the likely involvement of dopamine in the processes of learning and memory in the insect nervous system (Tempel et al, 1984;Budnik and White, 1988;Schafer and Rehder, 1989;Buchner, 1991;Nassel and Elekes, 1992). Further, genetic studies on dopamine receptor mutants in Drosophila could identify the physiological roles of the separate activation of each of the two second messenger systems potentially coupled to the DopR99B receptor, because a variation in the local G-protein environment of different cell types expressing this receptor might allow the receptor to be coupled differently in different cell types.…”

“…Evidence also is accumulating for an important role for dopamine in learning and memory and in neuronal development in insects (Tempel et al, 1984;Budnik and White, 1988;Budnik et al, 1989;Buchner, 1991). However, very little information is available on dopamine receptors and their modes of action in insects.…”

A primordial dopamine D1‐like adenylyl cyclase‐linked receptor from Drosophila melanogaster displaying poor affinity for benzazepines

“…Dopaminergic neurons and pathways have, in particular, been well mapped by glyoxylic acid-induced histofluorescence and immunohistochemistry in the CNS of Drosophila melanogaster [24,25]. A role for dopamine as a neurotransmitter has not been clearly defined in Drosophila CNS; however, alterations in the synthesis of dopamine and/or serotonin by mutants genetically deficient in dopa decarboxylase (DDC) appear to result in pertubations of learning [26]. Several well-characterized genetic mutations prominently expressed in the mushroom bodies affect learning and memory, such as dunce (a cAMP phosphodiesterase), rutabaga (a Ca2+/calmodulin-sensitive adenylyl cyclase), and DCO (protein kinase A catalytic subunit) [27].…”