Neurotrophic actions of dopamine on the development of a serotonergic feeding circuit in Drosophila melanogaster

Both decreased and increased neuronal dopamine levels in late embryogenesis during development of this circuit result in depressed levels of larval feeding. Perturbations in neuronal dopamine during this developmental period also result in greater branch complexity of the serotonergic fibers innervating the gut, as well as increased size and number of the serotonin-containing vesicles along the neurite length. This neurotrophic action for dopamine is modulated by the D2 dopamine receptor expressed during late embryogenesis in central 5-HT neurons. Animals carrying transgenic RNAi constructs to knock down both dopamine and serotonin synthesis in the central nervous system display normal feeding and fiber architecture. However, disparate levels of neuronal dopamine and serotonin during development of the circuit result in abnormal gut fiber architecture and feeding behavior.These results suggest that dopamine can exert a direct trophic influence on the development of a specific neural circuit, and that dopamine and serotonin may interact with each other to generate the neural architecture necessary for normal function of the circuit.Classical neurotransmitters can function as growth factors in developing neural tissues before adopting their roles as signaling molecules in the mature nervous system, and thus can exert pleiotropic effects on nervous tissue function [1,2]. Impaired neuronal signaling arising from developmental perturbations has been strongly implicated in the etiology of depression [3,4], and autism spectrum disorders [5]. Specifically, deficiencies in developmental dopamine (DA) signaling contribute to numerous psychiatric symptoms [6], and DA dysfunction plays a critical role in the onset of schizophrenia [7]. Developmental abnormalities in serotonin (5-HT) pathways have also been implicated in schizophrenia [8] as well as in autism [9,10].Elegant studies by Lauder and Kater and colleagues demonstrated that altered DA or 5-HT levels during embryogenesi