A trophic role for serotonin in the development of a simple feeding circuit.

Correct differentiation and positioning of individual synapses during development is fundamental to the normal function of neuronal circuits. While classical transmitters such as serotonin (5-HT) play a critical trophic role in neurogenesis in addition to their functions as transmitters in the mature nervous system, this process is not well understood. We used a simple model to assess both development and function of a specific behavioral circuit in the larval stage of the fruit fly (Drosophila melanogaster). We show that, as in all other species examined, the neurotransmitter actions of 5-HT depress feeding, and decreased neuronal 5-HT levels increase appetite. However, using transgenic tools, we show that constitutive knockdown of neuronal 5-HT synthesis to reduce 5-HT levels during central nervous system (CNS) development results in increased branching of the serotonergic fibers projecting to the gut, as well as increased size and number of varicosities along the neurite length. As larvae, these animals display decreased feeding rates relative to controls, and, when given exogenous 5-hydroxytryptophan, feeding is significantly enhanced. Late-stage wild-type embryos exposed to 5-HT to augment 5-HT levels during CNS development display, as mature larvae, a significant decrease in gut fiber branching and total varicosity number, as well as increased feeding and a hyposensitivity to the effects of 5-HT. Exposure of embryos unable to synthesize neuronal serotonin to 5-HT during late embryogenesis results in rescue of the feeding behavior and abnormalities in the 5-HT gut fiber architecture. These results demonstrate an inverse relationship between developmental 5-HT levels and complexity of the fiber architecture projecting to gut tissue, which results in a perturbed feeding pattern. We conclude that 5-HT is tightly regulated during CNS development to direct the normal architecture and mature function of this neural circuit. Copyright 2010 S. Karger AG, Basel.