Big Lessons from Tiny Flies: Drosophila melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

Abstract

The brain of Drosophila melanogaster is comprised of some 100,000 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g., motor activity, reward and aversion, memory formation, feeding, sexual appetite, etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference, etc. Flies harboring mutated human orthologs provide models which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput.

Development on Citrus medica infected with ‘Candidatus Liberibacter asiaticus’ has sex-specific and -nonspecific impacts on adult Diaphorina citri and its endosymbionts

“…However, aromatic-L-amino-acid decarboxylase also catalyzes the conversion of 5-hydroxytryptophan to serotonin [139], and the precursor of 5-hydroxytryptophan, tryptophan, was more abundant in CLas-exposed D. citri than controls (Figs 5 and 6). Like dopamine, serotonin is a neurotransmitter that modulates a variety of behaviors and neurological processes, including feeding, sleep, circadian rhythms, locomotion, and memory [140]. Metabolism of the major excitatory neurotransmitter, glutamate, and major inhibitory neurotransmitter, 4-aminobutyrate (GABA) [141] may have also been altered.…”

Cre-assisted Fine-mapping of Neural Circuits using Orthogonal Split Inteins

“…Among the neurons generated by Type II NBs are several populations of dopaminergic neurons, identified by a Tyrosine Hydroxylase-specific Gal4 driver (TH-Gal4). Dopaminergic neurons are of considerable interest because of their roles in a variety of important neurobiological processes, including learning, sleep, and locomotion (for review see Kasture et al, 2018). The approximately 120-130 dopaminergic neurons in the Drosophila CNS are produced by diverse NBs and numerous reagents have been generated to selectively target them (Aso et al, 2014; Friggi-Grelin et al, 2003; Xie et al, 2018).…”

Cre-assisted fine-mapping of neural circuits using orthogonal split inteins

“…Among the neurons generated by Type II NBs are several populations of dopaminergic neurons, identified by a Tyrosine Hydroxylase-specific Gal4 driver (TH-Gal4). Dopaminergic neurons are of considerable interest because of their roles in a variety of important neurobiological processes, including learning, sleep, and locomotion (for review see Kasture et al, 2018). The approximately 120-130 dopaminergic neurons in the Drosophila CNS are produced by diverse NBs and numerous reagents have been generated to selectively target them (Aso et al, 2014;Friggi-Grelin et al, 2003;Xie et al, 2018).…”