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Biomedical subjects

Marla B Sokolowski

Publications and source records attributed to Marla B Sokolowski.

11 recordsLinked to original sources

Natural variation in Drosophila melanogaster diapause due to the insulin-regulated PI3-kinase.

This study links natural variation in a Drosophila melanogaster overwintering strategy, diapause, to the insulin-regulated phosphatidylinositol 3-kinase (PI3-kinase) gene, Dp110. Variation in diapause, a reproductive arrest, was associated with Dp110 by using Dp110 deletions and genomic rescue fragments in transgenic flies. Deletions of Dp110 increased the proportion of individuals in diapause, whereas expression of Dp110 in the nervous system, but not including the visual system, decreased it. The roles of phosphatidylinositol 3-kinase for both diapause in D. melanogaster and dauer formation in Caenorhabditis elegans suggest a conserved role for this kinase in both reproductive and developmental arrests in response to environmental stresses.

Animals↗

The neurogenetics and evolution of food-related behaviour.

All organisms must acquire nutrients from the ambient environment to survive. In animals, the need to eat has driven the evolution of a rich array of complex food-related behaviours that ensure appropriate nutrient intake in diverse niches. Here, we review some of the neural and genetic components that contribute to the regulation of food-related behaviour in invertebrates, with emphasis on mechanisms that are conserved throughout various taxa and activities. We focus on synthesizing neurobiological and genetic approaches into a neurogenetic framework that explains food-related behaviour as the product of interactions between neural substrates, genes and internal and external environments.

Adaptation, Physiological↗

The carrot, not the stick: appetitive rather than aversive gustatory stimuli support associative olfactory learning in individually assayed Drosophila larvae.

The ability to learn is universal among animals; we investigate associative learning between odors and "tastants" in larval Drosophila melanogaster. As biologically important gustatory stimuli, like sugars, salts, or bitter substances have many behavioral functions, we investigate not only their reinforcing function, but also their response-modulating and response-releasing function. Concerning the response-releasing function, larvae are attracted by fructose and repelled by sodium chloride and quinine; also, fructose increases, but salt and quinine suppress feeding. However, none of these stimuli has a nonassociative, modulatory effect on olfactory choice behavior. Finally, only fructose but neither salt nor quinine has a reinforcing effect in associative olfactory learning. This implies that the response-releasing, response-modulating and reinforcing functions of these tastants are dissociated on the behavioral level. These results open the door to analyze how this dissociation is brought about on the cellular and molecular level; this should be facilitated by the cellular simplicity and genetic accessibility of the Drosophila larva.

Animals↗

Drosophila soluble guanylyl cyclase mutants exhibit increased foraging locomotion: behavioral and genomic investigations.

Genetic variation in the gene foraging (for) is associated with a natural behavioral dimorphism in the fruit fly, Drosophila melanogaster. Some larvae, called 'rovers', have increased foraging locomotion compared to others, called 'sitters', and this difference is directly related to for-encoded cGMP-dependent protein kinase (PKG) activity. Here we report that larvae with mutations in the gene dgcalpha1, which encodes a soluble guanylyl cyclase (sGC) subunit, have increases in both PKG activity and foraging locomotion. This is contrary to our original prediction that, based on the role of sGC in the synthesis of cGMP, dgcalpha1 mutant larvae would have deficient cGMP production leading to decreased PKG activation and thus reduced larval foraging locomotion. We performed DNA microarray analyses to compare transcriptional changes induced by a dgcalpha1 mutation in both rover and sitter wildtype genetic backgrounds. In either background, we identified many genes that are differentially transcribed, and interestingly, relatively few are affected in both backgrounds. Furthermore, several of these commonly affected genes are enhanced or suppressed in a background-dependent manner. Thus, genetic background has a critical influence on the molecular effects of this mutation. These findings will support future investigations of Drosophila foraging behavior.

Animals↗

Candidate genes for behavioural ecology.

In spite of millions of years of evolutionary divergence, the conservation of gene function is common across distant lineages. As such, genes that are known to influence behaviour in one organism are likely to influence similar behaviours in other organisms. Recent studies of the evolution of behaviour and morphological adaptation support this notion. Thus, the candidate gene approach offers great potential to expand our understanding of behavioural ecology. Changes in the expression of candidate genes can reveal their contribution to behavioural variation and/or phenotypic plasticity. Knowledge of gene function also enables experimental manipulation of behaviour in the lab and in the field. The candidate gene approach provides an accessible and useful tool for generating insights about animals that are not typically associated with genetic experimentation.

Journal Article↗

Behavioral genetics: guanylyl cyclase prompts worms to party.

When it comes to foraging, there are two types of worm in the world: those who enjoy a party, and those who prefer to dine alone. Two recent reports describe roles for guanylyl cyclase in the neuromolecular signaling systems that effect this natural behavioral dimorphism.

Animals↗

Refining GAL4-driven transgene expression in Drosophila with a GAL80 enhancer-trap.

We constructed an enhancer-trap element, P[GAL80], that encodes the yeast GAL80 repressor to refine expression of transgenes driven by the binary GAL4/UAS system. GAL80 blocks GAL4 activity by binding to its transcriptional activation domain. We screened GAL80 enhancer-traps for repression of GAL4-induced green fluorescent protein (GFP) in the intact larval nervous system. We selected one line that repressed GFP in a large set of cholinergic neurons. This line was used to refine GFP expression from a set of over 200 neurons to a subset of 20 neurons in a preselected GAL4 line. Expression of tetanus neurotoxin, a potent blocker of neurotransmitter release, in these 20 neurons reproduced an aberrant larval turning behavior previously assigned to the parental set of 200 neurons. Our results suggest that targeted GAL80 expression could become a useful means of spatially refining transgene expression in Drosophila.

Animals↗

NPY and the regulation of behavioral development.

Neuropeptide Y is implicated in the regulation of feeding in vertebrates, but recent studies in transgenic mice are contradictory. In this issue of Neuron, Wu et al. show a dual role for the Drosophila NPY (dNPF) in the developmental regulation of larval foraging and social behaviors, demonstrating a conserved role for this peptide in complex behaviors.

Animals↗

A drosophila model for attention deficit hyperactivity disorder (ADHD): No evidence of association with PRKG1 gene.

Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow up studies have indicated that 22-33% of patients continue to suffer from ADHD during late adolescence and adulthood. The action of psychostimulant drugs may be determined by additional mechanisms beyond the dopamine transporter and receptors. We are exploring new methodology for discovering these mechanisms. For example, in Drosophila, such an additional determinant of psychostimulant action could be protein kinase G (PKG) that affects food-search behavior. Here we initiated studies with the human homologue of PKG, the PRKG1 gene. The aim of this study was to investigate for the presence of linkage disequilibrium between the protein kinase G gene (PRKG1) and adult ADHD in a sample of nuclear families. Genotyping data for the C2276T polymorphism were analyzed using the Transmission Disequilibrium Test (TDT). Sixty three nuclear families were informative for the TDT on C2276T polymorphism, which showed no preferential transmission of either allele (chi-square = 0.778, df = 1, p = 0.316). These findings exclude a direct involvement of this genetic marker of the Protein kinase G gene in the pathogenesis of ADHD.

Animals↗

Activity of cGMP-dependent protein kinase (PKG) affects sucrose responsiveness and habituation in Drosophila melanogaster.

The cGMP-dependent protein kinase (PKG) has many cellular functions in vertebrates and insects that affect complex behaviors such as locomotion and foraging. The foraging (for) gene encodes a PKG in Drosophila melanogaster. Here, we demonstrate a function for the for gene in sensory responsiveness and nonassociative learning. Larvae of the natural variant sitter (for(s)) show less locomotor activity during feeding and have a lower PKG activity than rover (for(R)) larvae. We used rover and sitter adult flies to test whether PKG activity affects (1) responsiveness to sucrose stimuli applied to the front tarsi, and (2) habituation of proboscis extension after repeated sucrose stimulation. To determine whether the differences observed resulted from variation in the for gene, we also tested for(s2), a sitter mutant produced on a rover genetic background. We found that rovers (for(R)) were more responsive to sucrose than sitters (for(s) and for(s2)) at 1-, 2-, and 3-wk old. This was true for both sexes. Differences in sucrose responsiveness between rovers and sitters were greater after 2 h of food deprivation than after 24 h. Of flies with similar sucrose responsiveness, for(R) rovers showed less habituation and generalization of habituation than for(s) and for(s2) sitters. These results show that the PKG encoded by for independently affects sensory responsiveness and habituation in Drosophila melanogaster.

Animals↗